Cognitive neurosciences

While numerous maladies are associated with hypobaric hypoxia, muscle protein loss is an important under studied topic. Hence, the present study was designed to investigate the mechanism of muscle protein loss at HH. SD rats were divided into normoxic rats, while remaining rats were exposed to simulated hypoxia equivalent to 282-torr pressure (equal to an altitude of 7620 m, 8% oxygen), at 25 °C for 6, 12, and 24 h. Post-exposure rats were sacrificed and analysis was performed. Ergo, muscle loss-related changes were observed at 12 and 24 h post-HH exposure. An increased reactive oxygen species production and decreased thiol content was observed in HHexposed rats. This disturbance caused substantial protein oxidative modification in the form of protein carbonyl content and advanced oxidation protein products. The analysis showed increase levels of bityrosine, oxidized tryptophan, lysine conjugate, lysine conjugate with MDA, protein hydroperoxide, and protein-MDA product. These changes were also in agreement with increase in lipid hydroperoxides and MDA content. HSP-70 and HSP-60 were upregulated significantly, and this finding is corroborated with increase in ER stress biomarker, GRP-78. Overloading of cells with misfolded proteins further activated degradative machinery. Consequently, pro-apoptotic signaling cascade, caspase-3, and C/EBP homologous protein were also activated in 24-h HH exposure. Release of tryptophan and tyrosine was also increased with 24-h HH exposure, indicated protein degradation. Elevation in resting intracellular calcium ion, [Ca 2+ ]i, was also observed at 12-and 24-h HH exposure. The present study provides a detailed mechanistic representation of muscle protein loss during HH exposure. Keywords High altitude . Hypobaric hypoxia (HH) . Protein modifications . Muscle loss, proteostasis . Calcium Abbreviations HH Hypobaric hypoxia GRP Glucose regulating protein HSP Heat shock protein AOPP Advanced oxidation protein product MDA Malondialdehyde * Richa Rathor

Hypobaric hypoxia, a condition of low oxygen availability at high altitude, has a great impact on health via producing oxidative stress which could lead to protein modifications and skeletal muscle damage. Enhanced calpain activity has a major role in hypobaric hypoxia induced protein modifications and protein degradation in the skeletal muscle. The pilot study was designed to investigate the role of a calpain inhibitor, calpeptin in amelioration of hypoxia induced skeletal muscle damage. Male Sprague Dawley rats were exposed to hypobaric hypoxia (HH) with and without calpeptin (50 µg/kg, ip) treatment. HH exposure was given for 6 h at 25,000 ft. Following exposure, the animals were sacrificed and hind limb skeletal muscle was excised for analysis. Calpeptin administration inhibited protein oxidation (decrease protein carbonyl and AOPP content). Decrease in oxidized tryptophan and bityrosine content was also observed in calpeptin pre-treated group in comparison to HH exposed group. ...

While numerous maladies are associated with hypobaric hypoxia, muscle protein loss is an important under studied topic. Hence, the present study was designed to investigate the mechanism of muscle protein loss at HH. SD rats were divided into normoxic rats, while remaining rats were exposed to simulated hypoxia equivalent to 282-torr pressure (equal to an altitude of 7620 m, 8% oxygen), at 25 °C for 6, 12, and 24 h. Post-exposure rats were sacrificed and analysis was performed. Ergo, muscle loss-related changes were observed at 12 and 24 h post-HH exposure. An increased reactive oxygen species production and decreased thiol content was observed in HH-exposed rats. This disturbance caused substantial protein oxidative modification in the form of protein carbonyl content and advanced oxidation protein products. The analysis showed increase levels of bityrosine, oxidized tryptophan, lysine conjugate, lysine conjugate with MDA, protein hydroperoxide, and protein-MDA product. These chang...

 Chronic Hypobaric Hypoxia for 7 days causes deficits in spatial working memory.  HH resulted in the synaptic dysregulation of Kalirin 7 in the dorsal hippocampus of rat.  HH induces significant decrease in the Kalirin 7 expression in the CA1, CA3 & DG region of the hippocampus.

Visually controlled spatial memory is closely related to the visual system. The ganglionic layer of the retina is involved in the formation of visually controlled spatial memory. In glaucoma, as well as in Alzheimer's disease (AD), destruction of the neuronal apparatus of the ganglionic layer of the retina is observed. Recently, close attention has been paid to the role and importance of natural antioxidants in the prevention and treatment of these diseases. Our experiments were carried out on old male albino rats. Two groups of rats were studied: 1st group of naive rats did not receive curcuma (curcuma administration); the 2nd group of rats received curcuma for 30 days before the training. The first part of the experiment involved training albino rats in the Morris water maze. The pool filled with water and milk had a diameter of 102 sm. During the training, we recorded the duration of the latent period of the search for a hidden platform and the trajectory of movements relative to each trained animal. At the initial stage of navigational training, the latent period of searching for a hidden platform in both groups of trained animals was 90–120 s. Navigation training was carried out for 7 days. With each day of training, a reduction in the duration and trajectory of movements in the search for a hidden platform was observed. At the end of training, the duration of the latent period decreased from 120 s. up to 2–5 s. In order to create an experimental model of AD at the second stage of the experiment, we performed a surgical operation on bilateral bulbectomy (BB). The third stage of the experiment consisted of testing all experimental groups of animals 1.5 - 2 months after BB in the water maze. The results recorded during the testing showed that the latent period of the search for a hidden platform in the rats of the control group increased to 120–180 s. This fact was consistent with the results that had previously been obtained in naive animals. This fact reliably indicates that the animals forgot the location of the platform. In the behavior of rats, manifestations of such reactions as grooming, rearing, and the release of 2–5 boluses (characteristic of the initial stage of learning) were again observed. These data indicate that the visually controlled spatial memory was completely impaired in the rats in the control group. This indicates that the AD model was created. Testing a group of animals that received curcuma before training and surgery for BB allowed us to record a significant reduction in the duration of the latent period of searching for a hidden platform to 3–5 seconds. These rats were characterized by accelerated search behavior, lack of grooming, rearing, and bolus release. Therefore, spatial memory in curcuma-treated rats was not impaired. This means that it was not possible to create an experimental model of AD on them, in contrast to the control group of animals.

Visually controlled spatial memory is one of the most important cognitive processes studied by physiology and neuropsychology. An important role in the formation of spatial memory is played by the visual system, exactly, the retina (its ninth layer, represented by axons of ganglion cells). Evaluation of spatial memory in laboratories is carried out through the use of special tests. In our laboratory, experiments were carried out on two groups of animals. I – control group (naive rats); II group – rats that have saffron administration before training. The first stage of the experiment consisted in the formation of visually controlled spatial memory in albino rats using the method of the Morris water maze (1982). During the experiment, we measured the latent period of searching for a hidden platform for each trained animal. The duration of the search for the hidden platform was shortened every day (in parallel with the trajectory of movement of the trained animals in the water space). At the second stage of the experiment, in order to create an experimental analogue of Alzheimer's disease (AD), a surgical operation was performed on bilateral total bulbectomy. 1.5-2 months after the operation, the rats were tested for the preservation of cognitive
functions and visually controlled spatial memory (the third stage). The test results showed that the rats of the control group searched for the platform for a longer time than even at the initial stage of training. During the search for the platform, the rats of the control group did not perform sectoral or diagonal movements. They only swam around the perimeter of the pool. In the behavior of the control animals, the same motor reactions (grooming, rearing, bolus release) were observed, the manifestation of which was characteristic of the initial stage of the trained rats. A conclusion is made about the violation of spatial memory in rats of the control group, in which it was possible to form a model of AD. At the same time, testing a group of rats that had saffron administration before train ing and bulbectomy surgery showed a significant reduction in the duration of the latent period of searching for a hidden platform and the swimming trajectory of these animals in the water maze. In rats of this group, there was no manifestation of behavioral anxiety reactions – grooming and rearing. There was also no allocation of boluses for memorizing the location of the platform. These observations confirm the fact that despite the surgical removal of the olfactory bulbs, spatial memory in rats that have saffron administration was not disturbed. On the basis of the generalization carried out, the following conclusion was made: it was not possible to create an experimental model of AD on albino rats that received saffron before training and surgery. On the basis of the generalization carried out, the following conclusion was made: it was not possible to create an experimental model of AD on albino rats that received saffron before training and surgery. It has been proven that under the influence of saffron, despite the operation of bilateral total bulbectomy (usually leading to the creation of an experimental model of AD), the spatial memory of albino rats was not disturbed. This is a direct confirmation of the presence of a protective role of saffron in the formation of an experimental model of AD in animals.

Alzheimer xəstəliyi bütün dünyada geniş yayılmış neyrodegenerativ multifaktorial xəstəlikdir. 65-69 yaş arasında AX təxminən 1% təşkil edir və 85 yaşdan yuxarı insanlarda 50%-dən yüksəkdir. Son illərdə AX cavanlaşır": bütün xəstələrin 10%-i 33-60 yaş arasındadır, lakin AX-nin əksəriyyəti 80 yaş və yuxarıdır. 2030-cu ildə 65,7 milyon, 2050-ci ildə isə 115,4 milyon insanın demensiya ilə yaşayacağı təxmin edilir ki, bu da qlobal ictimai sağlamlıq və sosial rifah üçün son dərəcə ciddi bir yük deməkdir. Kimyəvi olaraq diferuloilmetan kimi tanınan Hindistan ədviyyatı sarıkökdə Curcuma longa) sarı piqment olan kurkumin ilk dəfə düz iki əsr əvvəl 1815-ci ildə iki Alman alimi Vogel və Pelletier tərəfindən təcrid edilmişdir. Kurkuminin təsiri insanlarda nevroloji xəstəliklərdə, xüsusilə AX və depressiyada tədqiq edilmişdir. Tədqiqat işi çəkisi 250-300 q olan 5 erkək albinos siçovulunun üzərində aparılmışdır. Morris su labirintinin içərisində hündürlüyü 45 sm, diametri 12 sm olan kiçik platforma yerləşdirilmişdir. Morris labirinti (diametri 102 sm) 25°C temperaturda su ilə doldurulmuşdur. Su albinos siçovulları üçün stres mənbəyidir. Az miqdarda süd tozu su ilə qarışdırılaraq Morris labirintinə əlavə edilmişdir. Süd tozu ilə qarışdırılmış suda görünməmək üçün ağ rəngli platforma istifadə edilmişdir. Platforma suyun səviyyəsindən 2 sm aşağıda yerləşməlidir. Siçovul hovuzun perimetri ətrafında üzür, çıxış yolu tapmağa çalışır. Platformanı tapdıqdan sonra siçovul “gruming” və “rearing” kimi davranış reaksiyalarını yerinə yetirir. “Rearing” zamanı siçovul məkan orientasiyası üçün və məkan yaddaşının formalaşması üçün pəncərədən gələn günəş işığını və divardakı şəkilləri yadda saxlayır. Bununla yanaşı, heyvanlar boluslarla feromonları ifraz edirlər. Morris metodunun yaddaşın öyrənilməsinin digər üsullarından fərqli üstünlüyü bundan ibarətdir: ifraz olunmuş boluslar eksperimentator tərəfindən hovuzdan çıxarılır ki, bu da feromonların axtarışını mümkünsüz edir. Beləliklə, məkan oriyentirlərə əsaslanan həqiqi məkan yaddaşı (naviqasiya) və davranış formalaşır. Təlimdən əvvəl siçovullara 20 gün müddətində sarıkökün məhlulu verilmişdir. Siçovullar suya baş vurduqda dərhal çıxış axtarırlar. Əvvəl perimetr boyunca daha sonra isə sektrorlara doğru hərəkət edirlər. Bir həftə boyunca keçirilən təlimin sonunda latent dövr 120 saniyədən 10-20 saniyəyə qədər qısalır. Tədqiqatımızın sonrakı mərhələsində ikitərəfli bulbektomiya cərrahi əməliyyatı yerinə yetirilmişdir. Əməliyyatdan üç ay keçdikdən sonra Morris su labirintində siçovulların məkan yaddaşının yoxlanılması üçün test aparılmışdır. Sarıkökün heyvanların beyninə prorektiv effekt göstərdiyi məlum olmuşdur. Nəticələr göstərmişdir ki, siçovulların təlimdən əvvəl sarıkökün məhlulu qəbul etməsi sarıkökün protektiv təsirinə görə Alzheimer xəstəliyini modelinin yaradılmasının qarşısını almışdır. Təbii antioksidantlar AX ilə əlaqəli zehni geriləmənin qarşısının alınması və müalicəsində ümumi proqramın bir hissəsi kimi böyük potensiala malikdir. Tərkibində böyük miqdarda selen olan təbii antioksidant sarıkökün qoruyucu funksiyaya malik olduğu və beyin neyronlarının məhv edilməsinin qarşısını aldığı təklif edilir.

Background: The therapeutic potential of medicinal plants in neurological health has gained attention. Acalypha wilkesiana, or Red Acalypha, has traditionally been used for anti-inflammatory, antimicrobial, and wound-healing properties. The hippocampus, a key brain region for memory, learning, and spatial navigation, is vulnerable to damage, making it a focus for studying natural compounds' effects on cognitive health. Damage to the hippocampus can impair cognitive abilities, emphasizing the need for interventions to prevent neurodegeneration. Methods: This study assessed Acalypha's effects on hippocampal health in rats. Four groups of seven rats each were used. The control group received distilled water, while the other groups were given Acalypha extracts at doses of 100 mg/kg, 200 mg/kg, or 400 mg/kg orally for 28 days after a 14day acclimatization. The study measured body weight, spatial memory using the Morris water maze, oxidative stress markers (superoxide dismutase [SOD], glutathione [GSH], catalase [CAT], malondialdehyde [MDA]), and hippocampal histology. Results: Relative to the control, Acalypha treatment significantly (p < 0.05) improved multiple parameters, including mitigating weight loss, enhancing spatial memory performance in the Morris water maze test, and reducing oxidative stress markers such as SOD, GSH, CAT, and MDA in a dosedependent manner. Additionally, it provided neuroprotection to the hippocampus, as evidenced by a reduction in vacuolation compared to the control group. Conclusions: Acalypha demonstrated notable neuroprotective effects, improving memory and reducing oxidative stress. This suggests its potential as a therapeutic agent for preserving hippocampal health and enhancing cognitive function, particularly against neurodegenerative conditions.

La Théorie des Fils d'Information postule l'existence d'un réseau immatériel reliant toutes les entités de l'univers par des flux d'information indépendants des supports matériels conventionnels. Ce réseau, constitué de fils interconnectés, transcende les limitations de l'espace-temps et pourrait expliquer des phénomènes allant de la transmission de pensées aux corrélations quantiques, en passant par le paradoxe de l'information des trous noirs. Nous proposons un cadre mathématique formel, des prédictions testables et des implications expérimentales en physique quantique, astrophysique et neurosciences. Cette théorie s'inscrit dans une démarche interdisciplinaire visant à relier la physique théorique, la cosmologie et les sciences cognitives pour mieux comprendre le rôle fondamental de l'information dans l'univers.

17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body weight gain. This study aimed to better understand the interferences that could exist between 17β-estradiol, D2 receptors and the selection of carbohydrate, fat and protein consumption, as well as their consequences on body weight gain by using an animal model of the menopause. Ovariectomy exacerbates the consumption of foods rich in lipids. Thus confirming an inhibitory action of 17β-estradiol (E2) on the consumption of these types of foods. This consumption stimulates body weight gain, which is promoted by the high caloric content of these foods and not by the amount consumed. Our results showed a direct involvement of D2 receptors in food choice. This choice would be made according to the two (2) isoforms of the D2 receptors. The D2/BR isoform directs towards a high carbohydrate consumption, without causing a gain in body weight. While D2/SUL, promotes high fat food consumption, causing an increase in body weight. In women, 17β-estradiol modulates the activity ratio between these two D2 receptor isoforms to ensure energy and homeostatic balance, stabilizing food intake and body weight.

Objective: Trimethyltin (TMT) chloride is an organotin compound used in industry. It has been linked to generating
reactive oxygen species (ROS), inflammatory processes, and neuronal death. Carvacrol is a monoterpene phenol
found in the Lamiaceae plant family, modulating inflammatory conditions and necroptosis in neural tissue. This study
aimed to investigate the neuroprotective effects of carvacrol in a rat model of hippocampal neuronal injury induced
by TMT.
Materials and Methods: In this experimental study, sixty male Wistar rats were randomly divided into five groups
(n=12): group 1 receiving saline, group 2 received dimethyl sulfoxide (DMSO) as a vehicle for 21 days, group 3 receiving
a single dose of TMT (8 mg/kg) and groups 4 and 5 receiving carvacrol 40 and 70 mg/kg daily for 21 days after a single
dose of TMT. All injections were intraperitoneal (I.P.). Caspase-3, Bax, Bcl-2, and Bdnf gene expression and the number
of pyknotic neurons in the hippocampus were quantified. Spatial memory was assessed with a radial arm maze.
Results: Statistical analysis of histological data revealed the carvacrol significantly attenuated cognitive dysfunction and
the number of pyknotic neurons in the hippocampal CA1 region of rats treated with TMT. Based on real-time polymerase
chain reaction (PCR), carvacrol modulated the expression of genes involved in apoptosis (Bax and Caspase-3) and
upregulated anti-apoptotic (Bcl-2) and brain derived neurotrophic factor (Bdnf) genes in the hippocampal tissue.
Conclusion: These findings revealed neuroprotective effects of carvacrol which might be mediated by apoptotic and
anti-apopetotic factors.

Introduction The objective of this systematic review was to synthesise the evidence for cognitive strategy training to determine its effectiveness to improve performance of activities of daily living in an adult neurological population. Method Medline, CINAHL, EMBASE, PSYCInfo, PsycBITE and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched until August 2019. Studies examining the effect of cognitive strategy training on functional performance were included. Population criteria included adults with non-progressive neurological conditions. External and internal validity of included studies was systematically evaluated using an appropriate methodological quality assessment for each study design. A content analysis was conducted of the methodologies used. Findings Forty-one studies met the inclusion criteria and were appraised for content, 16 randomised or quasi-randomised trials were meta-analysed. Trial quality was generally ‘good...

Neuroprotection is a mechanism within the central nervous system (CNS) that protects neurons from damage as a result of a severe insult. It is known that growth hormone (GH) is involved in cell survival and may inhibit apoptosis in several cell types, including those of the CNS. Both GH and GH-receptor (GHR) genes are expressed in the cerebellum. Thus, we investigated the possible neuroprotective role of GH in this organ, which is very sensitive to hypoxic/ischemic conditions. Endogenous GH levels increased in the brain and cerebellum (30% and 74%, respectively) of 15-day-old chicken embryos exposed to hypoxia during 24 h compared to normoxia. In primary embryonic cerebellar neuron cultures treated under hypoxia (0.5% O 2) and low glucose (1 g/L) conditions (HLG) for 1 h, GH levels increased 1.16-fold compared to the control. The addition of 1 nM recombinant chicken GH (rcGH) to cultures during HLG increased cell viability (1.7-fold) and the expression of Bcl-2 (1.67-fold); in contrast the caspase-3 activity and the proportion of apoptotic cells decreased (37% and 54.2%, respectively) compared to HLG. rcGH activated the PI3K/Akt pathway both under normoxic and HLG conditions, increasing the proportion of phosphorylated Akt (1.7-and 1.4-fold, respectively). These effects were abolished by wortmannin and by immunoneutralization, indicating that GH acts through this signaling pathway. Furthermore, the 15-kDa GH variant (10 nM) significantly increased cell viability and decreased caspase-3 activity during HLG condition. Thus GH may act as a paracrine/autocrine neuroprotective factor that preserves cellular viability and inhibits apoptotic cell death.

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-a, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

The antioxidant and antiradical properties of the tetra nitrosyl iron complex with thiosulfate ligands (TNIC) were studied in vitro in mouse brain homogenates. It was found for the first time that TNIC is an effective antioxidant. The effect of TNIC on the catalytic activity of mitochondrial enzymes cytochrome c oxidase and monoamine oxidase A was studied. It was shown for the first time that TNIC is an inhibitor of the catalytic activity of cytochrome c oxidase and monoamine oxidase A in animal brain mitochondria in vitro.

Exposure to high-altitude results in hypobaric hypoxia which is considered as an acute physiological stress. This condition often leads to high-altitude illnesses such as highaltitude cerebral edema, high altitude pulmonary edema and hypoxic muscle weakness. Hypoxic injuries can be prevented by either preconditioning with cobalt chloride or treatment with drugs. The aim of current investigation was to evaluate the effect of naringenin (NGEN) and quercetin (QUR) against behavioral impairment and neuronal damage in hypoxia induced murine model. An oral administration of NGEN or QUR (10 mg/kg each) was given to the animal prior to every hypoxic treatment. Behavioral changes were evaluated along with the hypoxia exposure for all the groups. After hypoxia exposure and drug administration, the mice were euthanized; brains were harvested and stored for further analysis. Expressions of hypoxia induced proteins were ensured by Western blotting. Our results demonstrate expression of hypoxia inducible factor 1a (HIF1a), vascular endothelial growth factor (VEGF), active caspase 3 and ubiquitin levels were significantly reduced upon drug treatment. However, expressions of chaperones (Hsp70, Hsp90 and C-terminus Hsp70 interacting protein) were moderately changed. We established our findings based on behavioral test, hematoxylin and eosin as well as amino-cupric silver stainings. In addition, the protective nature of these drugs was corroborated with immunoblot and immunofluorescence results, where we confirmed the down regulation of caspase 3 and ubiquitinated proteins. To conclude, treatment with NGEN and QUR alone substantially ameliorated hypoxia induced brain dysfunction and acts like a neuroprotectant.

This study examined the protective effect of quercetin against high-altitude-induced brain damage in rats. A molecular docking study was performed to investigate the potential effect of quercetin in reducing brain damages through its ability to target the oxidative stress enzymes. Biomarker assessment screening assays were also performed then followed by in vivo studies. Three groups of rats were divided into the control group, an untreated animal model group with induced brain damage, and finally, the quercetin treated group that received quercetin dose equal to 20 mg/kg of their body weights. Molecular docking studies and biomarker assessment screening assays proved the potential effect of quercetin to affect the level of representative biomarkers glutathione (GSH), glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). Additionally, the protective effect of quercetin against...

The aim of this study was to analyze the effects of chronic oxidative stress on mitochondrial function and its relationship to progressive neurodegeneration in the hippocampus of rats chronically exposed to ozone. Animals were exposed to 0.25 ppm ozone for 7, 15, 30, or 60 days. Each group was tested for (1) protein oxidation and, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx) and succinate dehydrogenase (SDH) activity using spectrophotometric techniques, (2) oxygen consumption, (3) cytochrome c, inducible nitric oxide synthase (iNOS), peroxisome proliferator-activated receptor c Co-activator 1a (PGC-1a), B-cell lymphoma (Bcl-2), and Bax expression using Western blotting, (4) histology using hematoxylin and eosin staining, and (5) mitochondrial structure using electron microscopy. Our results showed increased levels of carbonyl protein and Mn-SOD activity after 30 days of ozone exposure and decreased GPx activity. The SDH activity decreased from 7 to 60 days of exposure. The oxygen consumption decreased at 60 days. Western blotting showed an increase in cytochrome c at 60 days of ozone exposure and an increase in iNOS up to 60 days of ozone exposure. The expression of PGC-1a was decreased after 15, 30, and 60 days compared to the earlier time Bcl-2 was increased at 60 days compared to earlier time points, and Bax was increased after 30 and 60 days of exposure compared to earlier time points. We observed cellular damage, and mitochondrial swelling with a loss of mitochondrial cristae after 60 days of exposure. These changes suggest that low doses of ozone caused mitochondrial abnormalities that may lead to cell damage.

Background: Selenium (Se) had underscored many beneficial neuroprotective potentials, particularly with respect to learning and memory. However, the protective effect of Se in memory impairment associated with Chronic Restraint Stress (CRS) is not yet elucidated. Aim of Study: The present study was carried out to examine the effect of Se treatment against CRS induced behavioral and biochemical abnormalities. Material and Methods: The stress was induced by restraining the animals in well ventilated tubes (6h/d) for consecutive 21 days. Animals were randomly divided into 4 groups (8 rats each): Normal control, drug control, CRS and Se treated CRS groups. After 21 days of the experiment, memory function was evaluated by Passive Avoidance (PA), T-maze and object recognition tasks. Hippocampal oxidative stress markers, Brain Derived Neurotrophic Factor (BDNF), amyloid P (AR) protein, phosphorylated TAU (p-TAU) protein as well as glutamate and acetylcholinestrase activity (AchE) levels were assessed. Results: This study revealed that the memory performance was markedly deteriorated in CRS group, accompanied by noticeable alterations in hippocampal oxidative stress markers, depleted levels of BDNF together with overproduction of A P , p-TAU and glutamate as well as, excessive activity of AchE enzyme. Meanwhile, these behavioral and biochemical deviations were alleviated under 21 days of Se co-treatment in CRS exposed rats. Conclusion: This study proved the beneficial protective effects of Se in CRS-induced memory deficits and its associated pathological changes in rats, which may draw the attention to Se as a new therapeutic candidate for memory dysfunction associated with stress and its related disorders.

Introduction: The concept of neuroprotection gaining considerable interest in search for novel therapy that has potential to preserve brain tissues and improve cognitive functions in ischemic brain damage. In the present study we evaluated the neuroprotective efficacy of hydro alcoholic extract of Vanda roxburghii in experimental models of ischemic hippocampal injury in rats. Materials and Methods: Ischemic hippocampal injury was induced by single intra-hippocampal injection of Endothelin-1 (80μM) using stereotaxic instrument. Following ischemic hippocampal damage, hydro alcoholic extract of Vanda roxburghii (HAVR) (200 and 400mg/kg) was administered orally, once in a day for 14 consecutive days. Results and Discussion: The Morris water maze, Actophotometer and Open field behavioral test results showed significant cognitive deficit after ischemic hippocampal damage, however the repeated administration of HAVR at higher dose level for 14 consecutive days attenuated the cognitive deficits to a significant level. The histopathological examination of CA1 and CA3 regions of hippocampus revealed the loss of normal pyramidal cells and degenerative changes with shrunken, hyperdensed soma with pyknotic nuclei, however HAVR treatment at both dose levels significantly attenuated the observed qualitative changes. HAVR treatment showed significant anti-oxidant properties by inhibiting lipid peroxidation in ischemic condition as well as restoration of glutathione peroxidase enzymes to significant level. Conclusion: The study concludes that V. roxburghii extract and its constituents have neuroprotective potentials in ischemic hippocampal injury.

Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test...

Background: The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization. Results: Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. Conclusion: The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected

Prolonged chronic stress causing elevated plasma glucocorticoids leads to neurodegeneration. Adaptation to stress (allostasis) through neuroprotective mechanisms can delay this process. Studies on hippocampal neurons have identified carboxypeptidase E (CPE) as a novel neuroprotective protein that acts extracellularly, independent of its enzymatic activity, although the mechanism of action is unclear. Here, we aim to determine if CPE plays a neuroprotective role in allostasis in mouse hippocampus during chronic restraint stress (CRS), and the molecular mechanisms involved. Quantitative RT-PCR/in situ hybridization and Western blots were used to assay for mRNA and protein. After mild CRS (1 h/d for 7 d), CPE protein and mRNA were significantly elevated in the hippocampal CA3 region, compared to naïve littermates. In addition, luciferase reporter assays identified a functional glucocorticoid regulatory element within the cpe promoter that mediated the up-regulation of CPE expression in...

Background: The neurocycle model has been developed based on cognitive neuroscience studies and can be applied to manage the functioning of the mind. Objectives: The present study investigated the effectiveness of the neurocycle mind-management approach in the resiliency and wellbeing of female university students. Materials & Methods: This single-subject experimental study was conducted based on the AB model. The research population comprised all single female university students aged 20 to 30 years studying at Khatam University in 2022. The participants were 3 students who attended the training intervention, and one was the control. The study data were collected using Connor and Davidson's (2003) resilience scale and Ryff's (1989) psychological wellbeing scale. Data analysis was performed through chart analysis, clinical improvement rate, and reliable change index. Results: The obtained data revealed that the students' resilience and psychological wellbeing scores increased compared to the baseline and control values. The overall improvement rates of the participants in terms of resilience and psychological wellbeing were 45.23% and 43.89%, respectively, though not clinically significant. In all three participants, the reliable change index in both variables was higher than 1.96, so the impact of the intervention was statistically significant. Based on the follow-up phase results, the effects of the intervention increased after 1 month from the last intervention session, but the improvement was not significant. Conclusion: The neurocycle mind-management technique can be explored and used as an effective intervention to improve female university students' resilience and psychological wellbeing.

Previous studies demonstrated that the Western diet (WD), which is rich in saturated fat (HFD) and refined sugar (HSU), is related to the impairments of hippocampus-dependent learning and memory and forebrain synaptic plasticity in rodents. The environmental enrichment (EE) has been shown to enhance learning and memory in the HFD-induced cognitive deficits, but the exact mechanism is still not clearly understood. Therefore, the present study aimed to clarify the effects of the EE on spatial memory in WD-fed rats, and to analyze the potential role of corticosteroid receptors in the EE conditioning. Main methods: Male Wistar albino rats were housed in either an enriched or standard environment and fed with the HFD (35% of energy as fat), HSU (100% of carbohydrate as sucrose) or standard rat chow for 4 weeks. We used the Morris' water maze test (MWM) to assess the learning and memory performance, and measured plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH), as well as glucocorticoid (GR) and mineralocorticoid receptor (MR) levels in the hippocampus. Key findings: The results showed that HFD-fed rats displayed poorer learning and memory performance evaluated with MWM than controls. The EE reversed the cognitive deficits caused by the HFD. In addition, the EE resulted in an increase of GR and MR levels without affecting plasma CORT and ACTH concentrations. Significance: Based on these findings, it could be suggested that the EE plays an important role in amelioration of the HFD-induced cognitive impairments, but this intervention is independent of the hypothalamic-pituitaryadrenal axis and hippocampal corticosteroid receptor levels.

Resumen: Se describieron los principales hallazgos actuales relacionados con el proceso del envejecimiento. Para ello se realizó una revisión de artículos actualizados que abordan la temática. para valorar la necesidad de la educación en torno a esta etapa de la vida, desde la neuropsicología, en donde se enfatiza la importancia de un manejo integral, ya que se observa al individuo dentro de un contexto sociocultural que impacta en su funcionamiento cerebral. Conocer el desarrollo en el envejecimiento normal proporciona pautas para el abordaje integral del adulto mayor.

Background Datura metel (DM) stramonium is a medicinal plant often abused by Nigerians due to its psychostimulatory properties. Hallucinations, confusion, agitation, aggressiveness, anxiety, and restlessness are reported amongst DM users. Earlier studies suggest that DM induces neurotoxicity and affect brain physiology. However, the exact neurological effects of DM extract in the medial prefrontal cortex (mPFC) and hippocampal morphology have not been elucidated. In this study, we evaluated the hypothesis that oral exposure to DM extract exerts a neurotoxic effect by increasing oxidative stress in the mPFC and the hippocampus and induces behavioral deficits in mice. Results DM methanolic extract exposure significantly increased MDA and NO levels and reduced SOD, GSH, GPx and CAT activities in mice brains. In addition, our results showed that DM exposure produced cognitive deficits, anxiety, and depressive-like behaviour in mice following oral exposure for 28 days. Moreover, the mPFC...

Antecedentes: El estudio de las funciones ejecutivas en personas que perpetran delitos como el homicidio agravado ha tomado un creciente interés en la neurociencia, más aún en el marco del conflicto armado. Objetivo: La presente investigación cuantitativa busca describir el desempeño que un grupo de desmovilizados de las AUC con antecedentes de homicidio agravado, tienen frente a pruebas que miden juicio moral (dilemas de Heinz personales e impersonales, test de la mirada de Baron-Cohen) y las funciones ejecutivas de actualización (FAS, K-BIT, fig de Rey), alternancia (Torre de Hanoi y WSCT) e inhibición (Torre de Hanoi y Stroop). Metodología: Mediante un muestreo no probabilístico por conveniencia se seleccionaron 17 desmovilizados de las AUC con antecedentes de homicidio agravado, las evaluaciones fueron hechas en la cárcel o en otras instalaciones siempre bajo la custodia del INPEC. Resultados: Los resultados permiten concluir que la muestra no presenta alteración en funciones ej...

In our study, we tried to find whether changes in expressions of inducible nitric oxide synthase (iNOS), corticosteroid (gluco-and mineralocorticoid) receptors (GRs and MRs, respectively), and bcl 2 protein within the early stages of streptozotocin (STZ)-induced diabetes in Wistar rats can be involved in hippocampal dysfunction. Expressions of iNOS and bcl 2 were studied using indirect immunofluorescence techniques, while GR and MR expressions were estimated using in situ mRNA hybridization. The concentrations of insulin, ACTH, and corticosterone in the blood serum were measured using ELISA kits. It was found that expression of iNOS in the CA2 and CA3 hippocampal areas increased significantly at day 3 after STZ injection, and corticosterone and ACTH levels in the serum increased at day 14. The iNOS expression was downregulated at day 14 of the development of diabetes. These changes were accompanied by significantly increased expression of GRs in the hippocampus. Neither bcl 2 nor MR expression increased in the CA2 and CA3 hippocampal areas within the examined period of the development of diabetes. Thus, we first obtained proof of noticeable early molecular events in the rat hippocampus related to experimental diabetes. These events may be linked with diabetes-associated cognitive decline observed in patients suffering from diabetes.

Neuroprotection is a mechanism within the central nervous system (CNS) that protects neurons from damage as a result of a severe insult. It is known that growth hormone (GH) is involved in cell survival and may inhibit apoptosis in several cell types, including those of the CNS. Both GH and GH-receptor (GHR) genes are expressed in the cerebellum. Thus, we investigated the possible neuroprotective role of GH in this organ, which is very sensitive to hypoxic/ischemic conditions. Endogenous GH levels increased in the brain and cerebellum (30% and 74%, respectively) of 15-day-old chicken embryos exposed to hypoxia during 24 h compared to normoxia. In primary embryonic cerebellar neuron cultures treated under hypoxia (0.5% O 2) and low glucose (1 g/L) conditions (HLG) for 1 h, GH levels increased 1.16-fold compared to the control. The addition of 1 nM recombinant chicken GH (rcGH) to cultures during HLG increased cell viability (1.7-fold) and the expression of Bcl-2 (1.67-fold); in contrast the caspase-3 activity and the proportion of apoptotic cells decreased (37% and 54.2%, respectively) compared to HLG. rcGH activated the PI3K/Akt pathway both under normoxic and HLG conditions, increasing the proportion of phosphorylated Akt (1.7-and 1.4-fold, respectively). These effects were abolished by wortmannin and by immunoneutralization, indicating that GH acts through this signaling pathway. Furthermore, the 15-kDa GH variant (10 nM) significantly increased cell viability and decreased caspase-3 activity during HLG condition. Thus GH may act as a paracrine/autocrine neuroprotective factor that preserves cellular viability and inhibits apoptotic cell death.

Background Datura metel (DM) stramonium is a medicinal plant often abused by Nigerians due to its psychostimulatory properties. Hallucinations, confusion, agitation, aggressiveness, anxiety, and restlessness are reported amongst DM users. Earlier studies suggest that DM induces neurotoxicity and affect brain physiology. However, the exact neurological effects of DM extract in the medial prefrontal cortex (mPFC) and hippocampal morphology have not been elucidated. In this study, we evaluated the hypothesis that oral exposure to DM extract exerts a neurotoxic effect by increasing oxidative stress in the mPFC and the hippocampus and induces behavioral deficits in mice. Results DM methanolic extract exposure significantly increased MDA and NO levels and reduced SOD, GSH, GPx and CAT activities in mice brains. In addition, our results showed that DM exposure produced cognitive deficits, anxiety, and depressive-like behaviour in mice following oral exposure for 28 days. Moreover, the mPFC...

The present study demonstrates the consequences of animal exposure to an enriched environment compared to animals living in a standard environment regarding learning and space memory. Male albino Wistar rats were exposed to an enriched environment for 4 weeks after the lactation period and tested in the Morris water maze in the distal and proximal clue version and in the arena. In the former test, the animals were tested at 50 days of age with 12 daily trials on two consecutive days. At the end of each session, scopolamine at the dose of 0.6 mg/kg/ml or saline solution was injected intraperitoneally. Twenty-eight days after the first phase, a new test consisting of a single trial was held (retest). An independent group of animals receiving no drug was subjected to the arena test and to the proximal clue version of the Morris maze. In the distal clue version the results did not show differences between groups in the first phase of the experiment. After 28 days (retest), the animals reared in a standard environment and treated with scopolamine exhibited a significant increase in latency compared to the group receiving the same drug and stimulated and to the group receiving saline. The arena data demonstrated a significant increase in exploratory activity in the group of animals reared in an enriched environment. The proximal clue version of the Morris maze did not show differences between groups. The results of the present study indicate that animals exposed to environmental enrichment react less to the amnesic effects of scopolamine and show an increase in exploratory activity.

Bacopa monniera (B.monniera) plant has been reported as nerve tonic and memory enhancer from ancient times in Indian system of medicine i.e. Ayurveda. The active components present in B.monniera are Bacoside-A & Bacopaside-II which are mainly responsible for its memory effects and other health benefits. Calcium gluconate (CG), organic calcium having available calcium (13 %) is one of best sources for calcium fortification in ice cream. In this study, B.monniera extract 10 mg/100g (Ethanol extraction) and calcium gluconate 217mg/100g was added to ice cream mix subjecting to ageing, freezing, hardening and storage. Sensory and physico-chemical analysis of the prepared product was carried out. HPLC analysis was carried out to confirm the presence of bacosides (Bacoside-A & Bacopaside-II) and to estimate the quantity of bacosides. Calcium content in fortified ice cream was 165 mg/100g where as control ice cream was 145 mg/100g.

Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management. Keywords Cerebral ischemia. Withania somnifera. Behavior. Oxidative stress. Mitochondrial dysfunctions. Apoptosis Abbreviations WS Withania somnifera IRI Ischemia reperfusion injury Bcl-2 B-cell lymphoma 2 Bax Bcl-2-associated X-protein

Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management. Keywords Cerebral ischemia. Withania somnifera. Behavior. Oxidative stress. Mitochondrial dysfunctions. Apoptosis Abbreviations WS Withania somnifera IRI Ischemia reperfusion injury Bcl-2 B-cell lymphoma 2 Bax Bcl-2-associated X-protein

The present work is to evaluate the neurotoxicity induced by pyrethroid insecticide &quot;Deltamethrin&quot; at 0.32 mg/kg/day in two main regions of the Wistar rat brain (hippocampus and striatum) and the protective effects of Quercetin at 10 mg/kg/day on this toxicity after 90 days of exposure. The assay of brain parameters showed that Deltamethrin caused a significant increase of mitochondrial metabolite level (proteins, lipids, and carbohydrates) and enzyme activity (glutathione S-transferase and superoxide dismutase); a decreased amount of mitochondrial glutathione level and catalase and glutathione peroxidase activities; and an increase of malondialdehyde (MDA) acid levels of the two regions. Furthermore, mitochondrial functional testing in the brains of treated rats exhibited a significant increase in permeability followed by a mitochondrial swelling. Instead, a statistically significant decrease in mitochondrial respiration (O2 consumption) was recorded in the striatum and h...

Zhen Tian Wan (ZTW), decoction consisting of seven herbs including Rhizoma ligustici,Radix Angelicae sinensis, Ledebouriella sesloides, Radix Angelica pubescentis, Flos carthami, Ramulus uncariae cumuncis and Radix Angelica dahuricae, has been widely used in traditional Chinese medicine (TCM) , as treatment for headaches, migraine, premenstrual syndrome (PMS), and in soothing the nervous systems. The objective of the study was to investigate the neuroprotective effects of the formula using the Pial-strip model and Morris water maze analysis in rats. Doses of 1600, 3200 and 6400 mg/kg body wt orally were used. Dihydroergocristine 0.4 mg/kg p.o was used as the reference standard. The contents of malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD) in the hippocampus and cortex were measured using thiobarbituric acid, nitrate reductase and xanthine-xanthine oxidase spectrophotometric methods, respectively. ZTW 1600- 6400mg/kg daily doses to pial s...

Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test...

Glutamate-induced excitotoxicity is one of the major underlying mechanisms for neurodegenerative diseases. Efforts are being made to treat such conditions with an array of natural compounds that can modulate the release of glutamate or the underlying mechanisms associated with it. Withania somnifera extract has potent pharmacologic activity similar to that of Korean Ginseng tea and is used to treat several neuronal disorders. However, to date, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders. Present study was carried out to investigate withanolide-A, one of the active constituents of Withania somnifera against glutamate-induced excitotoxicity in retinoic acid differentiated Neuro2a neuroblastoma cells. The results indicated that glutamate treatment for 2 h induced death in cells that was significantly attenuated by pre-treatment with MK-801 (specific NMDA receptor antagonist) and different concentrations of withanolide-...

Introduction The objective of this systematic review was to synthesise the evidence for cognitive strategy training to determine its effectiveness to improve performance of activities of daily living in an adult neurological population. Method Medline, CINAHL, EMBASE, PSYCInfo, PsycBITE and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched until August 2019. Studies examining the effect of cognitive strategy training on functional performance were included. Population criteria included adults with non-progressive neurological conditions. External and internal validity of included studies was systematically evaluated using an appropriate methodological quality assessment for each study design. A content analysis was conducted of the methodologies used. Findings Forty-one studies met the inclusion criteria and were appraised for content, 16 randomised or quasi-randomised trials were meta-analysed. Trial quality was generally ‘good...

We have previously shown that both acute and chronic ethanol treatment depresses neural activity, specifically in the cingulate cortex. Minor influences were found in the motor cortex. The acute effect of ethanol in the hippocampus was intermediate to those in the cingulate and motor cortices. In the present study, we concentrate on the chronic effects of ethanol on the hippocampus. We demonstrate how the neuronal activity underlying food-acquisition behavior is modified after chronic ethanol treatment, and how the hippocampus subserves formation of newly-formed alcohol-acquisition behavior. Neuronal activity in CA1 was more sensitive to chronic ethanol than the Dg area. Acute administration of ethanol had a normalizing effect on the chronically-treated animals: their performance and the hippocampal neural activity approached a normal range. The sets of neurons involved in food-acquisition behavior formed before chronic ethanol treatment, and those involved in alcohol-acquisition behavior formed after treatment significantly overlapped supporting the view that the neuronal mechanisms of pre-existing behavior provide the basis for the formation of new behavior. Additionally, we also discovered alcohol-acquisition selective neurons. Assuming that the formation of new neuronal specializations underlies learning, we believe that alcohol-selective neurons are specialized during the formation of alcohol-acquisition behavior. Our data demonstrate several new findings on the effect of acute and chronic ethanol on hippocampus activity, and how the neuronal activity relates to behavior before and after ethanol treatment.

The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pretreated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management. Keywords Cerebral ischemia Á Withania somnifera Á Antioxidant Á Behaviour Á Oxidative stress Abbreviations AChE Acetylcholinesterase WS Withania somnifera MDA Malondialdehyde T-SHs Total thiols LMW-SHs Low molecular weight thiols P-SHs Protein thiols TTC 2,3,5-triphenyltetrazolium chloride Electronic supplementary material The online version of this article (

Exposure to global hypoxia and ischemia has been reported to cause neurodegeneration in the hippocampus with CA3 neurons. This neuronal damage is progressive during the initial phase of exposure but maintains a plateau on prolonged exposure. The present study on Sprague Dawley rats aimed at understanding the underlying molecular and epigenetic mechanisms that lead to hypoxic adaptation of CA3 neurons on prolonged exposure to a global hypoxia. Our results show stagnancy in neurodegeneration in CA3 region beyond 14 days of chronic exposure to hypobaria simulating an altitude of 25,000 ft. Despite increased synaptosomal glutamate and higher expression of NR1 subunit of NMDA receptors, we observed decrease in post-synaptic density and accumulation of synaptic vesicles at the pre-synaptic terminals. Molecular investigations involving western blot and real-time PCR showed duration-dependent decrease in the expression of SNAP-25 resulting in reduced vesicular docking and synaptic remodelin...

Exposure to benzo[a]pyrene (B[a]P), a prototype of polycyclic aromatic hydrocarbons (PAHs) easily cross blood brain barrier (BBB) and is associated with impaired learning and memory in adult rats. However, there is no symmetric study reported on association between B[a]P exposure during the early development and hippocampal dendritic architecture causing behavioral changes like learning and memory deficit of adult rats. We investigated a fourteen day consecutive B[a]P administration, intraperitonial (i.p.), with two different doses (0.1 and 1μM) during early adolescence at PND30-44 and learning behavior assessed between PND 45-60 in adult male rats. The anxiolytic like behavioural analysis was done by LDPT. Depressive like behaviour was estimated through sucrose preference and learning and memory by T-maze. After B[a]P administration oxidative stress markers like glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), reduced (GSH) and oxidized glutathione (GSSG) were evaluated. To parallel these behavioral and antioxidant level changes to alteration in dendritic morphology, Golgi-Cox staining was performed in the hippocampus. Our study showed anxiolytic like behavioral response with significant increase in time spent in light zone and significant (p < 0.05) decrease in preference for sucrose and a reduction in percentage of spontaneous responses in T-maze test in B[a]P administered group as compared to vehicle control. B[a]P exposed male rats showed significant increase in GST activity (p < 0.05) and concentration of GSSG with a decay in GSH, GPx and GR in both the groups as compared to control. B[a]P administered rats showed significant loss in total dendritic length and number (28%) with reduced spine density (18%) in both higher and lower doses. These results suggested that B [a]P administration can be associated with an increase ROS production showing altered antioxidant defence system through glutathione biosynthesis and causing profound alterations in dendritic length and spine density of hippocampal neurons leading towards learning and memory deficits in adult rats.

High altitude (HA), defined as approximately 3000-5000 m, considerably alters physiological and psychological parameters within a few hours. Chronic HA-mediated hypoxia (5000 m) results in permanent neuronal damage to the human brain that persists for one year or longer, even after returning to sea level. At HA, there is a decrease in barometric pressure and a consequential reduction in the partial pressure of oxygen (PO2), an extreme environmental condition to which humans are occasionally exposed. This condition is referred to as hypobaric hypoxia (HBH), which represents the most unfavourable characteristics of HA. HBH causes the disruption of oxygen availability to tissue. However, no review article has explored the impact of HBH on cognitive functions or the potential therapeutic agents for HBH. Therefore, the present review aimed to describe the impact of HBH on both physiological and cognitive functions, specifically learning and memory. Finally, the potential therapeutic agen...

Hypoxia-ischemia (HI) is the main cause of mortality in the perinatal period and morbidity, in survivors, which is characterized by neurological disabilities. The immature brain is highly susceptible to hypoxicischemic insult and is responsive to environmental stimuli, such as environmental enrichment (EE). Previous results indicate that EE recovered memory deficits in adult rats without reversing hippocampal atrophy related to HI. The aim of this study was to investigate behavioral performance in the open field and rota-rod apparatuses, in object recognition and inhibitory avoidance tasks, as well as dendritic spine density in the hippocampus, in rats undergoing HI and exposed to EE. Seven-day old male rats were submitted to the HI procedure and divided into 4 groups: control maintained in standard environment (CTSE), controls submitted to EE (CTEE), HI in standard environment (HISE) and HI in EE (HIEE). Behavioral and morphological parameters were evaluated 9 weeks after the environmental stimulation. Results indicate impairment in the object recognition task after HI that was recovered by enrichment; however the aversive memory impairment in the inhibitory avoidance task shown by hypoxic-ischemic rats was independent of the environment condition. Hypoxic-ischemic groups showed more crossing responses during the first minute in the open field, when compared to controls, but no differences were found between experimental groups in the rotarod test. Dendritic spine density in the CA1 subfield of the right hippocampus (ipsilateral to the artery occlusion) was decreased after the HI insult, and increased in enriched controls; interestingly enriched HI rats did not differ from CTSE. In conclusion, EE was effective in recovering declarative memory impairment in object recognition and preserved hippocampal dendritic spine density loss after neonatal HI injury.