Papers by Fabiano M Cordova
Research, Society and Development, 2025
Experimental models of thiamine deficiency (TD) have primarily focused on male rodents, meaning t... more Experimental models of thiamine deficiency (TD) have primarily focused on male rodents, meaning that the effects of TD in females and the pathogenesis associated with neurological disorders remain unknown. This article aimed to present an investigation on the effects of TD with amprolium in female mice, evaluating metabolic and behavioral effects, as well as the modulation of ERK1/2 phosphorylation in the cerebral cortex and thalamus. Furthermore, we used the antioxidant Trolox and anti-inflammatory agent dimethyl sulfoxide to investigate the role of oxidative stress and neuroinflammation in this process. The animals were exposed to a thiamine-deficient diet with the additional administration of amprolium (60 mg/kg) for 20 days. After treatment, we observed a reduction in food consumption and animal body weight, with a decrease in motor coordination and exploratory activity, and, in parallel, an increase in the phosphorylation of ERK1/2, both in the cerebral cortex and thalamus in deficient animals. Deficient animals that received Trolox or dimethyl sulfoxide presented with attenuation of these effects, with the maintenance of motor coordination and total blockage of ERK1/2 activation. The results showed that female mice could be used as a valid TD model, compatible with other methods, showing important neurological changes. This study showed that in females, TD also involves mechanisms of oxidative stress and inflammation, responds positively, and can be used as a model animal.
Brazilian Journal of Veterinary Medicine, 2024
Three outbreaks of herpesvirus meningoencephalitis in cattle have been reported in three municipa... more Three outbreaks of herpesvirus meningoencephalitis in cattle have been reported in three municipalities in the northern region of the State of Tocantins, Brazil. In one outbreak, 41 predominantly young bovines were affected, with 2-3 deaths in some cases. The animals showed neurological signs of incoordination, blindness, and recumbency, with death occurring within approximately 4-5 d. At necropsy, hyperemia and leptomeningeal hemorrhages were observed in the brain. Histology revealed more intense lesions in the rostral portions of the brain, mainly affecting the frontoparietal cerebral cortex, with nonsuppurative encephalitis and meningitis, glial nodules, neuronophagia, and eosinophilic intranuclear inclusion bodies in the astrocytes and neurons. This study shows the presence of bovine herpesvirus in Tocantins, probably the highly neurotropic type 5 strain, and emphasizes its importance in the differential diagnosis of bovine neuropathies.
ERK1/2 modulation in the central nervous system of male and female thiamine-deficient mice with amprolium
Laboratory Animals, 2024
Thiamine deficiency experimental models focus on using the pyrithiamine analog in male rodents, m... more Thiamine deficiency experimental models focus on using the pyrithiamine analog in male rodents, making the thiamine deficiency effects in females and the use of other thiamine antagonists, such as amprolium, unknown. We investigated the impact of thiamine deficiency with amprolium in the cerebral cortex and thalamus of male and female mice by evaluating the modulation of ERK1/2 phosphorylation. The animals were exposed for 20 days to thiamine-deficient chow with different doses of amprolium (20, 40, 60 and 80 mg/kg) and at different treatment periods (five, 10, 15 or 20 days) at a dose of 60 mg/kg. After treatments, ERK1/2 phosphorylation was analyzed by western blot. In male mice, we observed a progressive increase in ERK1/2 phosphorylation in both the cerebral cortex and thalamus in response to the dose of amprolium. In females, ERK1/2 phosphorylation did not progressively increase in response to the amprolium dosage. However, an increase in phosphorylation at the higher doses of 60 and 80 mg/kg was observed. We observed a more intense increase in ERK1/2 phosphorylation in males’ cerebral cortex and thalamus from 10 days onwards. In females, the ERK1/2 modulation profiles were similar. The results show that thiamine deficiency induction with amprolium is efficient, compatible with other recognized models that use pyrithiamine, showing changes in cell signaling in the nervous system. The study showed differences in response to thiamine deficiency with amprolium between male and female mice in relation to ERK1/2 phosphorylation and demonstrated that females respond positively to the method and can also be used as model animals.
Brazilian Journal of Veterinary Pathology, 2022
This study aimed to evaluate the effects of stress in bovines submitted to emergency slaughter ca... more This study aimed to evaluate the effects of stress in bovines submitted to emergency slaughter caused by lengthy transportation
to slaughterhouses in the state of Tocantins, Brazil. Blood collections were performed individually during exsanguinations. Tissue
samples were obtained after evisceration on the slaughter line. The animals were divided into the Experimental Group (EG), with
19 bovines destined for immediate emergency slaughter, and the Control Group (CG), with 24 bovines slaughtered normally at the
abattoir flow. The EG showed lower values of erythrocytes, hemoglobin, hematocrit, platelets, neutrophilia with band neutrophils,
and lymphopenia. Hyperalbuminemia, high levels of total proteins, glucose, and creatinine, and lower urea levels were observed in
the EG. The globulins were equal between the groups. Histopathology revealed hepatocytes with vacuolated cytoplasm (87.5% of
the cases) and liver congestion (83.33%). Interstitial emphysema (95.65%), alveolar emphysema (65.21%), and congestion (52.17%)
were observed in the lungs. The kidneys showed congestion (80.95%) and hyaline casts (100%). The spleens showed rarefaction
in the white (70%) and red pulp (65%), in addition to hemosiderosis (10%). This suggests that the animals transported over long
distances are submitted to severe stress, with water and food deprivation, resulting in hematological and biochemical changes, with
histological lesions and serious bruises affecting the musculoskeletal system. There is loss of homeostasis, severe debilitation, with
destination for emergency slaughter with the conditional use of meat for consumption
Thiamine deficiency and recovery: impact of recurrent episodes and beneficial effect of treatment with Trolox and dimethyl sulfoxide
Naunyn-Schmiedeberg's Archives of Pharmacology, 2021
Thiamine Deficiency Modulates p38MAPK and Heme Oxygenase-1 in Mouse Brain: Association with Early Tissue and Behavioral Changes
Neurochemical Research, 2020
Thiamine deficiency (TD) produces severe neurodegenerative lesions. Studies have suggested that p... more Thiamine deficiency (TD) produces severe neurodegenerative lesions. Studies have suggested that primary neurodegenerative events are associated with both oxidative stress and inflammation. Very little is known about the downstream effects on intracellular signaling pathways involved in neuronal death. The primary aim of this work was to evaluate the modulation of p38MAPK and the expression of heme oxygenase 1 (HO-1) in the central nervous system (CNS). Behavioral, metabolic, and morphological parameters were assessed. Mice were separated into six groups: control (Cont), TD with pyrithiamine (Ptd), TD with pyrithiamine and Trolox (Ptd + Tr), TD with pyrithiamine and dimethyl sulfoxide (Ptd + Dmso), Trolox (Tr) and DMSO (Dmso) control groups and treated for 9 days. Control groups received standard feed (AIN-93M), while TD groups received thiamine deficient feed (AIN-93DT). All the groups were subjected to behavioral tests, and CNS samples were collected for cell viability, histopathology and western blot analyses. The Ptd group showed a reduction in weight gain and feed intake, as well as a reduction in locomotor, grooming, and motor coordination activities. Also, Ptd group showed a robust increase in p38MAPK phosphorylation and mild HO-1 expression in the cerebral cortex and thalamus. The Ptd group showed a decreased cell viability, hemorrhage, spongiosis, and astrocytic swelling in the thalamus. Groups treated with Trolox and DMSO displayed diminished p38MAPK phosphorylation in both the structures, as well as attenuated thalamic lesions and behavioral activities. These data suggest that p38MAPK and HO-1 are involved in the TD-induced neurodegeneration in vivo, possibly modulated by oxidative stress and neuroinflammation.
Animal Models and Experimental Medicine, 2018
Background: Thiamine deficiency (TD) models have been developed, mainly using the thiamine analog... more Background: Thiamine deficiency (TD) models have been developed, mainly using the thiamine analog pyrithiamine. Other analogs have not been used in rodents. We aimed to evaluate the effects and mechanisms of intraperitoneal (ip) amproliuminduced TD in mice. We also evaluated the associated pathogenesis using antioxidant and anti-inflammatory compounds (Trolox, dimethyl sulfoxide).
Article history Thiamine is an essential cofactor for several cellular functions. Your deficiency... more Article history Thiamine is an essential cofactor for several cellular functions. Your deficiency results in important neurological disorders, with mechanisms and lesions not fully understood. The purpose of this work was to evaluate a thiamine deficiency through the model of oral administration of amprolium in mice. The animals, treated for 20 or 80 days, received amprolium in drinking water at doses of 10, 20, and 30 mg/mL (deficient groups A, B, and C, respectively). Deficient groups A and B showed reduction in body weight gain and performance changes in the open field (decreased distance and rearing, and increased grooming) and rotarod (reduced latency to fall) behavioural tests, when treated for 80 days. However, no histological changes were observed in the central nervous system. Moreover, group B animals exposed to amprolium developed proteinuria, with moderate tubular nephrosis, at 80 days. At the highest dose (group C) there was no interest to drink water. The data suggest that the use of oral amprolium in mice may be an interesting and viable model, when using adequate exposure times and doses. The amprolium induces thiamine deficiency progressively and moderately, which may be potentially useful for disturbed pathogenesis studies.
Congenital heart diseases are not commonly diagnosed in wild animals. It is not surprising that f... more Congenital heart diseases are not commonly diagnosed in wild animals. It is not surprising that few reports exist in the literature, so that prevalence of these anomalies is unknown in wild species. We report a case of a ventricular septal defect documented in a free-ranging crab-eating fox (Cerdocyon thous). This animal presented with rapid, labored breathing, and on physical examination, pulmonary crackles and a holosystolic murmur were auscultated. The echocardiogram with Doppler showed discontinuity of the dorsal section of the ventricular septum, which allowed a turbulent systolic flow to move from the left to the right ventricle. The postmortem examination confirmed the absence of a dorsal connection between the septum and the atrioventricular junction, and pronounced left ventricular myocardial dilation was observed on histopathology. To the authors' knowledge, this is the first report of a perimembranous ventricular septal defect in a crab-eating fox.
Parkinsonism & Related Disorders
This study describes for the first time a case of coligranulomatosis in broilers in the state of ... more This study describes for the first time a case of coligranulomatosis in broilers in the state of Tocantins. Three males from a farm (flock of approximately 300 birds), with approximately 60 days of age, were sent to the Veterinary Pathology Laboratory of the Universidade Federal do Tocantins. The birds were necropsied and tissue samples were sent for histopathology. Grossly, significant lesions were firm nodules, whitish gray, measuring from 3 to 10 mm in diameter located in the serosal surfaces of the intestines and gall bladder. Microscopically, typical granulomas with eosinophilic necrotic centers surrounded by epithelioid cells and multinucleated giant cells with scattered heterophils were observed. No mycotic forms or alcohol-acid resistant organisms were observed in sections stained by periodic acid-Schiff and Ziehl-Neelsen, respectively. Based on lesions was diagnosed coligranuloma, a rare form of avian colibacillosis.
Toxicology and Applied Pharmacology, 2002
Lead (Pb 2؉ ) is a cytotoxic metal ion whose mechanism of action is not established. However, Pb ... more Lead (Pb 2؉ ) is a cytotoxic metal ion whose mechanism of action is not established. However, Pb 2؉ is known to interact with a wide variety of molecules involved in signal transduction. In this study the effect of Pb 2؉ on protein phosphorylation in bovine adrenal chromaffin cells and human SH SY5Y cells was examined. Cells were incubated with 32 P i for 1 h in the presence of Pb 2؉ (1-10 M) and the proteins were separated by two-dimensional PAGE. An increase in the phosphorylation of a number of proteins was observed in response to Pb 2؉ , including three spots, MW 25 kDa, and pI's in the range 4.0 -4.5. These proteins were immunoidentified as three isoforms of the heat-shock protein 27 kDa (Hsp27), and the identity of the most basic spot was confirmed by amino acid sequencing. Phosphorylation of p38 MAPK was increased by Pb 2؉ and the effect of Pb 2؉ on Hsp27 phosphorylation was blocked by the p38 MAPK inhibitor SB203580 (1 M). The results were similar for bovine chromaffin cells and human SH SY5Y cells. This is the first report showing that Pb 2؉ can modulate the phosphorylation state of Hsp27 via activation of the p38 MAPK pathway. © 2002 Elsevier Science
Neuroscience, 2010
Physical exercise is a widely accepted behavioral strategy to enhance overall health, including m... more Physical exercise is a widely accepted behavioral strategy to enhance overall health, including mental function. However, there is controversial evidence showing brain mitochondrial dysfunction, oxidative damage and decreased neurotrophin levels after high-intensity exercise, which presumably worsens cognitive performance. Here we investigated learning and memory performance dependent on different brain regions, glutathione antioxidant system, and extracellular signal-regulated protein kinase 1/2 (ERK1/2), serine/threonine protein kinase (AKT), cAMP response element binding (CREB) and dopamine- and cyclic AMP-regulated phosphoprotein (DARPP)-32 signaling in adult Swiss mice submitted to 9 weeks of high-intensity exercise. The exercise did not alter the animals’ performance in the reference and working memory versions of the water maze task. On the other hand, we observed a significant impairment in the procedural memory (an implicit memory that depends on basal ganglia) accompanied by a reduced antioxidant capacity and ERK1/2 and CREB signaling in this region. In addition, we found increased striatal DARPP-32-Thr-75 phosphorylation in trained mice. These findings indicate an increased vulnerability of the striatum to high-intensity exercise associated with the disruption of implicit memory in mice and accompanied by alteration of signaling proteins involved in the plasticity of this brain structure.
Revista Brasileira de Ciência Veterinária, Dec 2012
The pre-stomach impaction is a rare digestive disorder. And can be primary or secondary origin. T... more The pre-stomach impaction is a rare digestive disorder. And can be primary or secondary origin. The authors describe the first report of impaction rumino-abomasal caused by eating stalk of banana (Musa sp.) In cattle. The cases occurred in two crossbred dairy cows, aged 5 and 4 years respectively, originated from a farm in the municipality of Araguaína, Tocantins (TO). The history, clinical findings, results of blood tests and analysis of rumen fluid led to diagnosis of compression of the rumen and abomasums, which were confirmed by necropsy and exploratory laparotomy. The use of stem of banana (Musa sp.) as the only source of forage favored the occurrence of impaction rumino-abomasal. However, this food source can be considered a good choice for cattle feed, from which is provided in adequate proportions in the diet.
Arquivos de Pesquisa Animal, 2013
The purpose of our retrospective study was to evaluate 85 histopathologic examinations performed ... more The purpose of our retrospective study was to evaluate 85 histopathologic examinations performed at the Laboratório de Patologia Veterinária (LPV) of the Escola de Medicina Veterinária e Zootecnina (EMVZ) of Universidade Federal do Tocantins (UFT) between the years 2008 and 2012 in cattle, sheep, horses, pigs and goats. Seventy one specimens were obtained during necropsy procedures and 14 from biopsies. The majority of tissue specimens (44/85) were sampled from cattle, followed by sheep (16/85), horses (16/85), pigs (5/85) and goats (4/85). A total of 4.7% of the tissue samples analyzed presented inconclusive results (2 from cattle, 1 from horse and 1 from sheep). The main systems affected were the digestive in cattle (12/44), tegumentary in horses (7/16) and reproductive in goats (2/4). Infectious diseases were diagnosed in 34 cases and the most frequent diagnostic was rabies, followed by pythiosis and pneumonia (5 cases respectively). Toxicosis was concluded in 15 cases with 13 being related to intoxication by ingestion of poisonous plants. Throughout the study we were able to identify the most significant diseases affecting farm animals at the studied region. Our results will serve as a guideline for identification of these clinical manifestations to the local farmers. That way, they will be able to plan better strategies regarding prevention; treatment and control of these diseases in order reduce economic losses as well as preventing sanitary embargos.
Neuroscience, 2013
L-DOPA alleviates the motor symptoms of Parkinson’s disease, but its long-term use is associated ... more L-DOPA alleviates the motor symptoms of Parkinson’s disease, but its long-term use is associated with undesirable dyskinesia. We now tested whether exercise can attenuate this L-DOPA-induced dyskinesia (LID). We tested the effects of exercise on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. Animals were treated with L-DOPA/benserazide (25/12.5 mg/kg, i.p.) without and with possibility to exercise (running wheel) during 2 weeks. Exercise drastically prevented the development of LID, and its associated aberrant striatal signaling, namely the hyperphosphorylation of dopamine and cAMP-regulated phosphoprotein 32 kDa protein and c-Fos expression. Our results indicate that exercise can partially prevent the development of LID through the normalization of striatopallidal dopaminergic signaling.
Brazilian Journal of Veterinary Pathology, Mar 10, 2014
The present experiment aimed to perform histopathological, muscle and liver glycogen and muscle p... more The present experiment aimed to perform histopathological, muscle and liver glycogen and muscle pH analyses of cows dead during transportation, and submitted to necropsy in slaughterhouses inspected by Federal Agencies, in Araguaína -TO, Brazil, from January to July 2013. Six affected animals dead during transportation and submitted to necropsy constituted the Experimental Group (EG); a Control Group (CG), was composed by 6 cows slaughtered ordinarily following the slaughter flow. Gross and histopathological evaluations were accomplished only on EG. The main gross lesions observed at necropsy were extensive subcutaneous and muscle hemorrhage and hematomas, interstitial (83.3% of cases) and alveolar (66.6% of cases) lung emphysema, lung congestion (66.6% of cases) and edema (16.6% of cases), kidney (83.3% of cases) and liver congestion (16.6% of cases). On histopathological evaluation, the lungs showed interstitial (100% of cases) and alveolar emphysema (66.6% of cases), congestion (66.6% of cases), edema (16.6% of cases) and blood aspiration (16.6% of cases). Renal congestion (83.3% of cases), hyaline casts (50% of cases) and tubular degeneration were the kidneys changes (16.6% of cases). Rarefaction of the white pulp (66.6% of cases), red pulp (66.6% of cases) and hemosiderin (16.6% of cases) were detected on spleen. The hepatocytes showed turve and finely vacuolyzed cytoplasm (lace-like aspect) possibly caused by a reduction on glycogen (50% of cases) and congestion (16.6% of cases). Autholysis was observed on 50% of the livers and 16.6% of the spleens and kidneys. The animals from the EG presented higher mean of degenerate muscle fibers. The intercostal muscle was more affected when compared with other muscles on the same group. Muscle pH values were higher on EG than on CG. Differently, glycogen average values were similar between groups (EG 58.97 µmol/g and CG 57.05 µmol/g). The results obtained in the present study allow to confirm that the cows, transported through long distances, and exposed to intense stress and water and food deprivation, show an homeostasis fall. Thus, stress and time of transportation affect glycogen concentrations and muscle pH. Bruises caused miofibrillar degeneration and hemorrhages that, when associated with loss of fluids through dehydration, lead to a clinical picture of hypovolemic shock evidenced by irreversible gross and microscopic changes causing death.
Equine Veterinary Education, 2015
Ependymoma is a rare tumour of the central nervous system that can vary in anatomical location an... more Ependymoma is a rare tumour of the central nervous system that can vary in anatomical location and produce a broad range of clinical signs. Sporadically described in dogs, cats, cattle and horses, this disease has never previously been reported in a mule. This report describes a case of a 12-year-old mule showing neurological signs, including blindness, dysphagia, incoordination, sternal recumbency, depression, apathy and emaciation. Because of the worsening health conditions, the animal was subjected to euthanasia for humane reasons. At necropsy, an area of malacia in the right subcortical region of the frontoparietal area of the cerebrum and an ovoid, firm, grey, 2.4 x 1.0 x 0.7 cm nodule in the right lateral ventricle was observed. Histopathology revealed that the nodule was a densely cellular mass with cells arranged in nests and cords, formations of pseudorosettes with perivascular deposition of fibrillar eosinophilic material and the presence of a few lymphocytes. The cells had rounded and moderately hyperchromatic nuclei, punctate chromatin, distinct nucleoli, and indistinct cytoplasmic margins. Based on the histopathological features, the nodule was diagnosed as an ependymoma, a tumour considered rare, but that may be included in the differential diagnosis for diseases with neurological signs.
Parkinsonism & Related Disorders
Developmental Brain Research, 2005
Thyroid hormone deficiency during the critical period of neural differentiation produces permanen... more Thyroid hormone deficiency during the critical period of neural differentiation produces permanent and severe alterations in the morphology and function of the nervous system leading to cretinism. Perinatal hypothyroidism results in permanent alterations of hippocampal synaptic functions in adult rats consequently causing learning and memory impairment. Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that regulate essential cellular activities ranging from gene expression, mitosis, programmed cell death to plasticity and memory formation, but their involvement in perinatal hypothyroidism is not determined. The present work was designed to investigate MAPKs phosphorylation in hippocampus of congenital neonatal hypothyroid rats. Congenital hypothyroidism promotes an increase in extracellular signal-regulated kinases 1/2 (ERK 1/2) phosphorylation (+50%) and a decrease in p38MAPK phosphorylation (50%) without changing in Jun N-terminal kinases (JNK) phosphorylation. Therefore, the congenital hypothyroidism model disturbs ERK 1/2 and p38MAPK phosphorylation pathways causing an important molecular alteration in the hippocampus. This event might be related, at least partially, to the deficits in hippocampal development and cognitive functions due neonatal congenital hypothyroidism.
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Papers by Fabiano M Cordova
to slaughterhouses in the state of Tocantins, Brazil. Blood collections were performed individually during exsanguinations. Tissue
samples were obtained after evisceration on the slaughter line. The animals were divided into the Experimental Group (EG), with
19 bovines destined for immediate emergency slaughter, and the Control Group (CG), with 24 bovines slaughtered normally at the
abattoir flow. The EG showed lower values of erythrocytes, hemoglobin, hematocrit, platelets, neutrophilia with band neutrophils,
and lymphopenia. Hyperalbuminemia, high levels of total proteins, glucose, and creatinine, and lower urea levels were observed in
the EG. The globulins were equal between the groups. Histopathology revealed hepatocytes with vacuolated cytoplasm (87.5% of
the cases) and liver congestion (83.33%). Interstitial emphysema (95.65%), alveolar emphysema (65.21%), and congestion (52.17%)
were observed in the lungs. The kidneys showed congestion (80.95%) and hyaline casts (100%). The spleens showed rarefaction
in the white (70%) and red pulp (65%), in addition to hemosiderosis (10%). This suggests that the animals transported over long
distances are submitted to severe stress, with water and food deprivation, resulting in hematological and biochemical changes, with
histological lesions and serious bruises affecting the musculoskeletal system. There is loss of homeostasis, severe debilitation, with
destination for emergency slaughter with the conditional use of meat for consumption