Anti-stress Effect of Octopus Cephalotocin in Rats

Molecular Neurobiology, 2003

The mechanisms that regulate neuronal function are a sum of genetically determined programs and experience. The effect of experience on neuronal function is particularly important during development, because early-life positive and adverse experience (stress) may influence the still "plastic" nervous system long-term. Specifically, for hippocampal-mediated learning and memory processes, acute stress may enhance synaptic efficacy and overall learning ability, and conversely, chronic or severe stress has been shown to be detrimental. The mechanisms that enable stress to act as this "double-edged sword" are unclear. Here, we discuss the molecular mediators of the stress response in the hippocampus with an emphasis on novel findings regarding the role of the neuropeptide known as corticotropin-releasing hormone (CRH). We highlight the physiological and pathological roles of this peptide in the developing hippocampus, and their relevance to the long-term effects of early-life experience on cognitive function during adulthood.

The Korean Journal of Physiology & Pharmacology, 2012

The hypothalamus-pituitary-adrenocortex (HPA) axis is the central mediator of the stress response. The supramammillary (SuM) region is relatively unique among the hypothalamic structures in that it sends a large, direct projection to the hippocampal formation. It has been shown that mild stress could activate the SuM cells that project to the hippocampus. However, the role of these cell populations in modulating the stress response is not known. The present study examined the effect of stress on different populations of SuM cells that project to the hippocampus by injecting the fluorescent retrograde tracer, fluorogold (FG), into the hippocampus and utilizing the immunohistochemistry of choline acetyltransferase (ChAT), corticotrophin releasing factor (CRF), serotonin (5-HT), glutamate decarboxylase (GAD), tyrosine hydroxylase (TH) and NADPH-d reactivity. Immobilization (IMO) stress (2 hr) produced an increase in the expression of ChAT-immunoreactivity, and tended to increase in CRF, 5-HT, GAD, TH-immunoreactivity and nitric oxide (NO)-reactivity in the SuM cells. Fifty-three percent of 5-HT, 31% of ChAT and 56% of CRF cells were double stained with retrograde cells from the hippocampus. By contrast, a few retrogradely labeled cells projecting to the hippocampus were immunoreactive for dopamine, γ-aminobutyric acid (GABA) and NO. These results suggest that the SuM region contains distinct cell populations that differentially respond to stress. In addition, the findings suggest that serotonergic, cholinergic and corticotropin releasing cells projecting to the hippocampus within the SuM nucleus may play an important role in modulating stress-related behaviors.

Basic and Clinical Neuroscience Journal, 2022

The lack of social communication is associated with the primary risk of proper brain functions. It is reported that crocin helps relieve this problem. The present study examined the protective effect of two doses of crocin on Long-term potentiation (LTP) of hippocampal cornu ammonis 1 (CA1) area as a cellular mechanism in rats exposed to chronic social isolated stress. Methods: Rats were assigned to the control, sham, isolation stress, and two stress groups (receiving 30 and 60 mg/kg crocin). Chronic isolation stress (CIS) was induced 6 h/d, and crocin was administrated for 21 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured by input/output functions and LTP induction in the CA1 area of the hippocampus. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. Results: The slope and amplitude of fEPSP severity were impaired in both input/output and LTP responses in the CIS group. Crocin at a dose of 30 and particularly 60 mg/kg improved input/output and LTP responses in the CIS group. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. In contrast, only a high dose of crocin decreased hippocampal corticosterone levels in the CIS condition. Finally, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups. Conclusion: The chronic isolation stress impaired neural excitability and Long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and Long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex.

Proceedings of the National Academy of Sciences, 2010

Stress affects the hippocampus, a brain region crucial for memory. In rodents, acute stress may reduce density of dendritic spines, the location of postsynaptic elements of excitatory synapses, and impair long-term potentiation and memory. Steroid stress hormones and neurotransmitters have been implicated in the underlying mechanisms, but the role of corticotropin-releasing hormone (CRH), a hypothalamic hormone also released during stress within hippocampus, has not been elucidated. In addition, the causal relationship of spine loss and memory defects after acute stress is unclear. We used transgenic mice that expressed YFP in hippocampal neurons and found that a 5-h stress resulted in profound loss of learning and memory. This deficit was associated with selective disruption of long-term potentiation and of dendritic spine integrity in commissural/associational pathways of hippocampal area CA3. The degree of memory deficit in individual mice correlated significantly with the reduced density of area CA3 apical dendritic spines in the same mice. Moreover, administration of the CRH receptor type 1 (CRFR 1 )blocker NBI 30775 directly into the brain prevented the stress-induced spine loss and restored the stress-impaired cognitive functions. We conclude that acute, hours-long stress impairs learning and memory via mechanisms that disrupt the integrity of hippocampal dendritic spines. In addition, establishing the contribution of hippocampal CRH-CRFR 1 signaling to these processes highlights the complexity of the orchestrated mechanisms by which stress impacts hippocampal structure and function.

Learning & memory (Cold Spring Harbor, N.Y.), 2015

Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal neurons. Structurally, human and animal studies have shown that stress changes neuronal morphology, suppresses neuronal proliferation, and reduces hippocampal volume. Since the inception of stress research nearly 80 years ago, much focus has been on the varying levels of hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine hormones, namely glucocorticoids, as mediators of the myriad stress effects on the hippocampus and as contributing factors to stress-associated psychopathologies such as post-traumatic stress disorder (PTSD). However, reports of glucocorticoid-produced alterations in hippocampal functioning vary widely across studies....

Brain Research, 2003

Journal of Neuroendocrinology, 2003

We examined the effects of acute and chronic stress on neurotransmission of nociceptin/orphanin FQ (N/OFQ) in a variety of brain regions. Four groups of rats were exposed to chronic variable stress, and/or a single acute stress before decapitation. Group 1 served as unstressed controls. The rats in group 2 (chronic stress/no acute stress) were exposed to a 10-day regimen of chronic stress (two unpredictable stressors per day). These rats were decapitated 20 h after the last stressor. The rats in group 3 (no chronic stress/acute stress) were not exposed to chronic stress, but they were restrained for 30 min prior to decapitation. The rats in group 4 (chronic stress/acute stress) were chronically stressed for 10 days, and were then restrained prior to decapitation. Trunk blood was collected, and plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) were assayed by radioimmunoassay (RIA). The rats' brains were dissected, and N/OFQ content was measured by RIA in a variety of brain regions, and in spinal cord. Chronic stress exposure altered the hormonal responses to the acute stress exposure. In the rats that were exposed to chronic stress without acute stress (group 2), N/OFQ content did not differ from the content of the unstressed controls in any of the dissected brain regions. In the two groups that were stressed acutely just before decapitation (groups 3 and 4), N/OFQ content was decreased by 25-30% in the basal forebrain. Accordingly, the neuronal content of N/OFQ is decreased in basal forebrain neurones during acute stress exposure. In light of our previous finding that N/OFQ administration increases circulating ACTH and CORT concentrations, and augments hormonal responses to an acute stressor, the current finding raises the possibility that endogenous N/OFQ participates in neuronal regulation of hormonal responses to acute stress exposure.

Neuroscience & Biobehavioral Reviews, 1996

consequences of intracerebral vasopressin and oxytocin: Focus on learning and memory. NEUROSCI BIOBEHAV REV 20(3)341-358, 1996.-Sincethe pioneering work of David de Wied and his colleagues, the neuropeptides arginine vasopressin and oxytocin have been thought to play a pivotal role in behavioral regulation in general, and in learning and memory in particular. The present review focuses on the behavioral effects of intracerebral arginine vasopressin and oxytocin,with particular emphasis on the role of these neuropeptides as signals in interneuronal communication. We also discuss several methodological approachesthat have been used to reveal the importance of these intracerebral neuropeptides as signals within signaling cascades. The hterature suggests that arginine vasopressin improves, and oxytoein impairs, learning and memory. However, a critical analysis of the subject indicates the necessity for a revision of this generalized concept. We suggest that, depending on the behavioral test and the brain area under study, these endogenous neuropeptides are differentially involved in behavioral regulation; thus, generalizations derived from a single behavioral task should be avoided. In particular, reeent studies on rodents indicate that sociallyrelevant behaviors triggered by olfactory stimuli and paradigms in which the animals have to cope with an intense stressor (e.g., foot-shock motivated active or passive avoidance) are controlled by both arginine vasopressin and oxytocin released intracerebrally.

Psychopharmacology, 2005

To investigate a possible link between some neuropeptides and depression, we analyzed their mRNA levels in brains of rats exposed to chronic mild stresses (CMS; a stress-induced anhedonia model), a commonly used model of depression. Rats exposed for 3 weeks to repeated, unpredictable, mild stressors exhibited an increased self-stimulation threshold, reflecting the development of an anhedonic state, which is regarded as an animal model of major depression. In situ hybridization was employed to monitor mRNA levels of neuropeptide Y (NPY), substance P and galanin in several brain regions. In the CMS rats, NPY mRNA expression levels were significantly decreased in the hippocampal dentate gyrus but increased in the arcuate nucleus. The substance P mRNA levels were increased in the anterodorsal part of the medial amygdaloid nucleus, in the ventromedial and dorsomedial hypothalamic nuclei and the lateral hypothalamic area, whereas galanin mRNA levels were decreased in the latter two regions. These findings suggest a possible involvement of these three peptides in mechanisms underlying depressive disorders and show that similar peptide changes previously demonstrated in genetic rat models also occur in the present stress-induced anhedonia model.

Frontiers in Cellular Neuroscience, 2014

In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8), which controls gamma-aminobutyric acid (GABA) neurotransmission through neuregulin-1 (NRG-1) and its receptor (ErbB4), is involved in neural plasticity . In the present study, we examined whether parvalbumin (PV)-positive neuronal networks, the majority of which are ErbB4-positive GABAergic interneurons, are controlled by neuropsin in tranquil and stimulated voluntarily behaving mice. Parvalbumin-immunoreactive fibers surrounding hippocampal pyramidal and granular neurons in mice reared in their home cage were decreased in neuropsin-deficient mice, suggesting that neuropsin controls PV immunoreactivity. One-or two-week exposures of wild mice to novel environments, in which they could behave freely and run voluntarily in a wheel resulted in a marked upregulation of both neuropsin mRNA and protein in the hippocampus. To elucidate the functional relevance of the increase in neuropsin during exposure to a rich environment, the intensities of PV-immunoreactive fibers were compared between neuropsin-deficient and wild-type (WT) mice under environmental stimuli. When mice were transferred into novel cages (large cages with toys), the intensity of PV-immunoreactive fibers increased in WT mice and neuropsin-deficient mice. Therefore, behavioral stimuli control a neuropsin-independent form of PV immunoreactivity. However, the neuropsindependent part of the change in PV-immunoreactive fibers may occur in the stimulated hippocampus because increased levels of neuropsin continued during these enriched conditions.