Animal Models Of Stress Research Articles

Stachyose Alleviates Corticosterone-Induced Long-Term Potentiation Impairment via the Gut-Brain Axis.

Stress can induce learning and memory impairment; corticosterone is often used to study the effects and mechanisms of stress in animal models. Long-term potentiation (LTP) has been widely used for tackling the mechanisms of memory. Liuwei Dihuang decoction-active fraction combination (LW-AFC) can improve stress-induced LTP and cognition impairment; stachyose is an oligosaccharide in LW-AFC. The effects and mechanisms of stachyose on stress are unknown. In this study, stachyose showed protective effects against LTP impairment by corticosterone in vivo only via intragastric administration for 7 consecutive days, but there was little effect even after direct intracerebroventricular injection; the protective effect of stachyose could be canceled by non-absorbable antibiotics (ATB) which disturbed gut flora. 16S rRNA sequencing, alpha diversity, and principal coordinate analysis (PCoA) revealed that the gut flora in corticosterone-treated mice was disturbed and stachyose could improve corticosterone-induced gut flora disturbance. Bacteroidetes were decreased and Deferribacteres were increased significantly in corticosterone-treated mice, and stachyose restored Bacteroidetes and Deferribacteres to the normal level. D-serine, a coactivator of NMDA receptors, plays an important role in synaptic plasticity and cognition. Here, corticosterone had little effect on the content of D-serine and L-serine (the precursor of D-serine), but it reduced the D-serine release-related proteins, Na+-independent alanine–serine–cysteine transporter-1 (ASC-1), and vesicle-associated membrane protein 2 (VAMP2) significantly in hippocampus; stachyose significantly increased ASC-1 and VAMP2 in corticosterone-treated mice, and ATB blocked stachyose’s effects on ASC-1 and VAMP2. NMDA receptors co-agonists L-serine, D-serine, and glycine significantly improved LTP impairment by corticosterone. These results indicated that stachyose might indirectly increase D-serine release through the gut–brain axis to improve LTP impairment by corticosterone in the hippocampus in vivo.

Development of an Animal Model of Military-Relevant Traumatic Stress.

Acute Stress Reactions (ASRs) affect a subgroup of individuals who experience traumatic stress. In the context of military operations, such reactions are often termed Combat and Operational Stress Reactions (COSRs). COSRs not only encompass all symptoms of ASRs but also include additional symptoms related to military combat and may develop at a rate higher than the general public experiences ASRs. Despite an obvious need, there are currently no approved pharmacologic treatments or guidelines for ASR and/or COSR. Preclinical rodent stress models and behavioral assessments are used to evaluate pharmacotherapies and elucidate underlying mechanisms. Here, we combined established traumatic stress models to develop a model of traumatic stress relevant to military trauma exposure and measured behavioral outcomes that reflect outcomes observed in ASRs and COSRs. Adult male rats underwent exposure to either a combination of two or three traumatic stress exposures (e.g., predator exposure, underwater trauma (UWT), and/or inescapable shock) or control procedures. Behavioral performance on the open field, elevated plus maze, and acoustic startle response (SR) was then assessed 24- and 48-hours following stress/control procedures. In Experiment 1, rats were exposed to a two-stressor model, where predator exposure was coupled with UWT. Minor behavioral deficits were observed in SR for stress-exposed rats as compared to controls. In Experiment 2, inescapable shock was added to predator exposure and UWT. Behavioral performance deficits were observed across all behavioral tests. In Experiment 3, procedures from Experiment 2 were repeated with the only major modification being a shortened predator exposure duration, which resulted in performance deficits in SR only. We found that the three-stressor model of Experiment 2 resulted in the greatest overall behavioral disturbance (both in the number of variables and magnitude of stress effects). Interestingly, behavioral deficits elicited from the shorter predator exposure were distinct from those observed with longer predator exposure times. Together, these results generally suggest that combined preclinical stressors with military-relevant elements result in behavioral performance deficits reflective of post-trauma phenotypes in Soldiers. The present findings support the use of both physical and psychological stressors to model operationally relevant traumatic stress exposure.

Long non-coding RNAs in Sus scrofa ileum under starvation stress.

ObjectiveIn this study, we aimed to identify long non-coding RNAs (lncRNAs) that play important roles in starvation stress, analyze their functions, and discover potential molecular targets to alleviate starvation stress to provide a theoretical reference for subsequent in-depth research.MethodsWe generated a piglet starvation stress animal model. Nine Yorkshire weaned piglets were randomly divided into a long-term starvation stress group (starved for 72 h), short-term starvation stress group (starved for 48 h), and the control group. LncRNA libraries were constructed using high-throughput sequencing of piglet ileums.ResultsWe obtained 11,792 lncRNAs, among which, 2,500 lncRNAs were novel. In total, 509 differentially expressed (DE)lncRNAs were identified in this study. Target genes of DElncRNAs were predicted via cis and trans interactions, and functional and pathway analyses were performed. Gene ontology functions and Kyoto encyclopedia of genes and genomes analysis revealed that lncRNA-targeted genes mainly participated in metabolic pathways, cellular processes, immune system processes, digestive systems, and transport activities. To reveal the mechanism underlying starvation stress, the interaction network between lncRNAs and their targets was constructed based on 26 DElncRNAs and 72 DEmRNAs. We performed an interaction network analysis of 121 DElncRNA–DEmRNA pairs with a Pearson correlation coefficient greater than 0.99.ConclusionWe found that MSTRG.19894.13, MSTRG.16726.3, and MSTRG.12176.1 might play important roles in starvation stress. This study not only generated a library of enriched lncRNAs in piglets, but its outcomes also provide a strong foundation to screen key lncRNAs involved in starvation stress and a reference for subsequent in-depth research.

Anti-TNF-α Therapy as a Potential Treatment for Comorbid Pain in Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs after exposure to a traumatic event. Chronic pain is one of the most frequent comorbidities for patients with PTSD and higher levels of the proinflammatory cytokine tumor necrosis factor α (TNF-α) have been detected in these patients. In a recent study, Dib et al (2021) used the single prolonged stress (SPS) animal model of PTSD and blocked TNF-α with either thalidomide or anti-TNF-α antibody. This way, the authors prevented mechanical allodynia and thermal hyperalgesia in SPS-rats.

Investigation of efficacy of asenapine on passive avoidance learning and memory and oxidative stress in animal model of seizure-induced with pentylenetetrazole

Asenapine (ASE) has been used for treatment of bipolar disorder. There is also evidence that it may be useful in the treatment of neurodegenerative disorders. In this regard, the efficacy of ASE in an experimental model of seizure and memory impairment caused by seizures in rats has been investigated in the present study. Seizures in male Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)), and the anticonvulsant effect of ASE (0.5 and 1 mg/kg, i.p.) was evaluated. The effect on memory was assessed using passive avoidance (PA) test in a shuttle box apparatus. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Serum was isolated for oxidative stress assays (nitric oxide (NO), and glutathione (GSH)). Intraperitoneal injection of ASE decreased the mean number of myoclonic jerks and duration of generalized tonic clonic seizures (GTCS) and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, ASE caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that ASE was able to significantly increase GSH serum levels and significantly reduce NO serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of ASE in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Investigation of efficacy of asenapine on passive avoidance learning and memory and oxidative stress in animal model of seizure-induced with pentylenetetrazole

Asenapine (ASE) has been used for treatment of bipolar disorder. There is also evidence that it may be useful in the treatment of neurodegenerative disorders. In this regard, the efficacy of ASE in an experimental model of seizure and memory impairment caused by seizures in rats has been investigated in the present study. Seizures in male Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)), and the anticonvulsant effect of ASE (0.5 and 1 mg/kg, i.p.) was evaluated. The effect on memory was assessed using passive avoidance (PA) test in a shuttle box apparatus. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Serum was isolated for oxidative stress assays (nitric oxide (NO), and glutathione (GSH)). Intraperitoneal injection of ASE decreased the mean number of myoclonic jerks and duration of generalized tonic clonic seizures (GTCS) and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, ASE caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that ASE was able to significantly increase GSH serum levels and significantly reduce NO serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of ASE in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

In Vivo Antistress Effects of Synthetic Flavonoids in Mice: Behavioral and Biochemical Approach.

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones (F1–F6) and flavonols (OF1–OF6), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC50 of 31.46 ± 1.46 μg/mL and 25.54 ± 1.21 μg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC50 values of 174.24 ± 2.71 μg/mL and 122.33 ± 1.98 μg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.

Efficacy of a Product Containing Xyloglucan and Pea Protein on Intestinal Barrier Function in a Partial Restraint Stress Animal Model.

Functional abdominal bloating and distension (FABD) are common and frequent symptoms in patients with pre-existing gastrointestinal (GI) disorders. FABD is characterized by recurrent abdominal fullness and bloating. The pathophysiology of FABD is still unclear. However, the plausible mechanisms involved are small intestinal bacterial overgrowth (SIBO), imbalance of gut microbiota, visceral hypersensitivity, intestinal permeability alteration, and disruption of intestinal barrier function. Thus, the creation of a barrier on the wall of the intestine could represent an alternative therapeutic strategy to prevent FABD. This study aimed to investigate the effect of two natural substances, Xyloglucan (XG) and Pea-protein (PP), known for their mucosal-protective properties, in an in vivo model of Partial restraint-stress (PRS). Our results showed that the pre-treatment with a product containing XG and PP in stressed-rats was able to reduce the number of abdominal contractions and visceral hypersensitivity. Moreover, XG and PP were able to reduce intestinal permeability alteration, restoring tight-junctions (TJs) expression and decreased the lactulose–mannitol ratio, a quantitative marker used to measure intestinal permeability, compared to PRS-group. In conclusion, the data obtained revealed that the product containing XG and PP was able to restore the normal intestinal-barrier function; therefore, it could be considered a therapeutic strategy to manage FABD.

The Effects of Stress and Diet on the "Brain-Gut" and "Gut-Brain" Pathways in Animal Models of Stress and Depression.

Compelling evidence is building for the involvement of the complex, bidirectional communication axis between the gastrointestinal tract and the brain in neuropsychiatric disorders such as depression. With depression projected to be the number one health concern by 2030 and its pathophysiology yet to be fully elucidated, a comprehensive understanding of the interactions between environmental factors, such as stress and diet, with the neurobiology of depression is needed. In this review, the latest research on the effects of stress on the bidirectional connections between the brain and the gut across the most widely used animal models of stress and depression is summarised, followed by comparisons of the diversity and composition of the gut microbiota across animal models of stress and depression with possible implications for the gut–brain axis and the impact of dietary changes on these. The composition of the gut microbiota was consistently altered across the animal models investigated, although differences between each of the studies and models existed. Chronic stressors appeared to have negative effects on both brain and gut health, while supplementation with prebiotics and/or probiotics show promise in alleviating depression pathophysiology.

Vagus nerve stimulation modulates hippocampal inflammation caused by continuous stress in rats

BackgroundPrevious studies have shown that vagus nerve stimulation (VNS) can attenuate inflammatory responses in peripheral tissues and also improve some neurological disorders and cognitive function in the brain. However, it is not clear how VNS is involved in neuropathological processes in brain tissues. Here, we investigated the regulatory effects of VNS on the production of proinflammatory cytokines in the hippocampus of an animal model of continuous stress (CS).MethodsCS was induced by placing rats in cages immersed with water, and acute or chronic electrical stimulation was applied to the cervical vagus nerve of CS animals. Protein levels in the gastric and hippocampal tissues were measured by western blotting and protein signals analyzed by immunofluorescence staining. von Frey test and forced swimming test were performed to assess pain sensitivity and depressive-like behavior in rats, respectively.ResultsLevels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues were significantly increased in CS animals compared to the untreated control and downregulated by acute VNS (aVNS). Iba-1-labeled microglial cells in the hippocampus of CS animals revealed morphological features of activated inflammatory cells and then changed to a normal shape by VNS. VNS elevated hippocampal expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in CS animals, and pharmacological blockade of α7 nAChR increased the production of TNF-α, IL-1β, and IL-6, thus suppressing cholinergic anti-inflammatory activity that was mediated by VNS. Chronic VNS (cVNS) down-regulated the hippocampal production of active form of caspase 3 and 5-HT1A receptors and also decreased levels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues of CS animals. Pain sensitivity and depressive-like behavior, which were increased by CS, were improved by cVNS.ConclusionsOur data suggest that VNS may be involved in modulating pathophysiological processes caused by CS in the brain.

Probing the antioxidant potential of Juglans regia (walnut) against arthritis-induced oxidative stress in Sprague Dawley rats.

Oxidative stress is the underlying cause of various chronic diseases and can contribute to its progression. Plant-based therapeutics are effective in the prevention of various chronic diseases through the management of underlying causes. Walnuts owing to their rich phytochemistry possess antioxidative potential. In this context, the present research was designed to explore the therapeutic potential of walnut against arthritis-induced oxidative stress in rat model. Purposely, 50 Sprague Dawley rats were separated into five groups of 10 rats each. The rats were categorized as G0 (negative control), G1 (positive control), G2 (methotrexate), G3 (walnut feed), and G4 (walnut extract). Walnut feed and extract significantly reduced oxidative stress by improving the antioxidant enzymes in arthritic rats. Total oxidative stress was reduced by 41.44% and 21.52% in G3 while 52.81% and 36.76% in G4 when compared with G1 and G2 , respectively. Antioxidant enzyme levels in serum were significantly improved after the walnut-based interventions. Evidently, superoxide dismutase level improved by 74.5% in G3 and 83.40% in G4 , while catalase level increased by 51.99% in G3 and 61.34% in G4 , respectively, when compared with G1 . Liver function biomarkers, that is, ALP and AST, were decreased in G3 and G4 when compared with G1 and G2 . The histopathological examination illustrated the promising role of walnut-based interventions in conserving the structural integrity of hepatic and renal tissues. Meanwhile, gene expression analysis revealed that walnut treatments protected from oxidative damage by the downregulation of Dual-oxidases expression. Conclusively, walnut feed and extract might serve as potent antioxidant intervention with no potential side effects. PRACTICAL APPLICATIONS: The present work was aimed to evaluate the efficacy of walnut-based interventions against arthritis-induced oxidative stress. The walnut-based interventions positively modulated the antioxidant enzymes, liver, and kidney functions, while downregulating the gene associated with oxidative stress in animal model. Consequently, the current findings suggest wider applications of walnuts to avoid free radical induced damage during arthritis; however, human intervention studies may be carried out to further understand the mechanism of their bioefficacy.

Pharmahuasca and DMT Rescue ROS Production and Differentially Expressed Genes Observed after Predator and Psychosocial Stress: Relevance to Human PTSD.

Post-traumatic stress disorder (PTSD) is associated with cognitive deficits, oxidative stress, and inflammation. Animal models have recapitulated features of PTSD, but no comparative RNA sequencing analysis of differentially expressed genes (DEGs) in the brain between PTSD and animal models of traumatic stress has been carried out. We compared DEGs from the prefrontal cortex (PFC) of an established stress model to DEGs from the dorsolateral PFC (dlPFC) of humans. We observed a significant enrichment of rat DEGs in human PTSD and identified 20 overlapping DEGs, of which 17 (85%) are directionally concordant. N,N-dimethyltryptamine (DMT) is a known indirect antioxidant, anti-inflammatory, and neuroprotective compound with antidepressant and plasticity-facilitating effects. We tested the capacity of DMT, the monoamine oxidase inhibitor (MAOI) harmaline, and "pharmahuasca" (DMT + harmaline) to reduce reactive oxygen species (ROS) production and inflammatory gene expression and to modulate neuroplasticity-related gene expression in the model. We administered DMT (2 mg/kg IP), harmaline (1.5 mg/kg IP), pharmahuasca, or vehicle every other day for 5 days, following a 30 day stress regiment. We measured ROS production in the PFC and hippocampus (HC) by electron paramagnetic resonance spectroscopy and sequenced total mRNA in the PFC. We also performed in vitro assays to measure the affinity and efficacy of DMT and harmaline at 5HT2AR compared to 5-HT. DMT and pharmahuasca reduced ROS production in the PFC and HC, while harmaline had mixed effects. Treatments normalized 9, 12, and 14 overlapping DEGs, and pathway analysis implicated that genes were involved in ROS production, inflammation, growth factor signaling, neurotransmission, and neuroplasticity.

Variation in trauma-related behavioral effects using a preclinical rat model of three predator exposure stress

The underlying mechanisms of trauma-related disorders are challenging to discover and the disorders are difficult to treat, in part due to the complex and varied expressions of response to traumatic stress. These challenges will be easier to overcome as more is understood about the variability in response to trauma. Incorporating assessment of variability into animal models of traumatic stress may allow better translation to clinical research and treatment development. In this study, we characterized variability in behavioral responses following traumatic stress exposure using a predator exposure (PE) animal model. Elevated plus maze (EPM) and acoustic startle response (SR) were used to study avoidance and arousal symptoms in male Sprague–Dawley rats. Behavioral data were compared between control (n = 31) and predator-exposed (n = 30) rats. PE behavior was clustered using k-means principal components analysis. Four clusters and three distinct subgroups were identified and were characterized as avoidant (Cluster 4, 30%), moderately avoidant (Clusters 2 and 3, 49%), and unaffected (Cluster 1, 17%). These results demonstrate that rodent responses to PE are varied, similar to human presentations following traumatic stress, suggesting it may be possible to develop treatment strategies for varied symptom presentations using a preclinical animal model.

Low-dose S-ketamine exerts antidepressant-like effects via enhanced hippocampal synaptic plasticity in postpartum depression rats

Rapid antidepressant effects of S-ketamine have repeatedly been confirmed in patients with depression, as well as in chronic unpredictable mild stress (CUMS) animal models. However, the pharmacological study of S-ketamine for anti-postpartum depression has not been considered. In this study, the classical method of reproductive hormone withdrawal was used to construct a rat model of postpartum depression (PPD). Subsequently, the study evaluated the effects of low-dose S-ketamine on behavior and synaptic plasticity, which is related to depression, in the hippocampus of PPD rats. Multiple behavioral tests were used to evaluate depression-like behaviors in PPD models. Synaptic plasticity of the hippocampus can be demonstrated by Western blot, Golgi staining, transmission electron microscopy, and electrophysiological recording. Our study provides insight into the role of low-dose S-ketamine in antidepressant as well as antianxiety and indicates that maintaining synaptic plasticity is a key target for S-ketamine therapy for postpartum depression induced by reproductive hormone withdrawal.

Comparison of three methods for in vivo quantification of glutathione in tissues of hypertensive rats

Glutathione (γ-L-glutamyl-L-cysteinyl-glycine, GSH) is a tripeptide that is part of the antioxidant defense system and contributes to numerous redox-regulatory processes. In vivo, reduced GSH and oxidized glutathione disulfide (GSSG) are present in redox equilibrium and their ratio provides important information on the cellular redox state. Here, we compared three different methods for in vivo quantification of glutathione in tissues of hypertensive rats, an accepted animal model of oxidative stress. In the present study, we used hypertensive rats (infusion of 1 mg/kg/d angiotensin-II for 7 days) to determine the levels of reduced GSH and/or GSH/GSSG ratios in different tissue samples. We used an HPLC-based method with direct electrochemical detection (HPLC/ECD) and compared it with Ellman’s reagent (DTNB) dependent derivatization of reduced GSH to the GS-NTB adduct and free NTB (UV/Vis HPLC) as well as with a commercial GSH/GSSG assay (Oxiselect). Whereas all three methods indicated overall a decreased redox state in hypertensive rats, the assays based on HPLC/ECD and DTNB derivatization provided the most significant differences. We applied a direct, fast and sensitive method for electrochemical GSH detection in tissues from hypertensive animals, and confirmed its reliability for in vivo measurements by head-to-head comparison with two other established assays. The HPLC/ECD but not DTNB and Oxiselect assays yielded quantitative GSH data but all three assays reflected nicely the qualitative redox changes and functional impairment in hypertensive rats. However, especially our GSH/GSSG values are lower than reported by others pointing to problems in the work-up protocol.

Animal models of stress and stress-related neurocircuits: A comprehensive review

Stress is considered to be one of the common pathogenic factors leading to mental disorders. Acute severe stress events or chronic distress could lead to depression and psychiatric disorders. Therefore, the establishment of stress animal models in the laboratory to mimic the stress suffering in humans would be beneficial for better understanding the etiology and mechanisms underlying stress-induced mental disorders. In addition, the development of powerful tools such as optogenetics and chemogenetics has made more rapid progress to reveal the critical neural circuits in regulating the pathogenesis of stress-induced disorders. This review firstly summarized the well-established different types of stress animal models widely used in the laboratory including acute stress models, chronic stress models, models of surgical stress, drug-induced stress models, and genetic mutation-associated stress models. Moreover, we also summarized the latest progress in understanding the characteristics and mechanisms of stress-related neurocircuits that are critical for discovering novel therapeutic strategies for stress-induced mental disorders.

In Vivo Antidepressant Efficacy of 3-Substituted Thietane-1,1-dioxide Derivative - A Preliminary Study for Novel Anti-Depression Therapy in Neurological Disorders.

Psychosocial stress-induced depressive behavior is linked to the etiology of several neurological diseases viz., PTSD, and neurodegenerative disease like Alzheimer's Disease (AD). The repeated bouts of social stress defeat can be induced using Resident-Intruder- Paradigm (RIP) and Chronic Mild Social Stress (CMSS) animal models to assess the stress-induced depressive behavioral patterns. The aim of this study to examine the anti-depressive efficacy of 3-methoxythietane- 1,1-dioxide (N-14) in RIP models of behavioral alterations. In this study, we have used Sprague-Dawley rats in Resident-Intruder-Paradigm (RIP), where intruders interacted with residents Day 0 to Day +5 for 10 minutes to invoke CMSS in intruders and became defeated/submissive rats due to the depressive-like behavioral alterations in social activity, explorations, grooming, defense, aggressive behavior, social interaction, freeze, rearing etc., with residents. Control intact animals are included in group I, group II received N-14 alone; group III received CMSS, and group IV received cotreatment of N14 with CMSS. N-14 (2 mg/kg) was administered intraperitoneally from Day 0 to Day +5 to intact animals and intruder animals under conditions of CMSS. Several behavioral tests viz., forced swim test, open field test, and elevated-plus maze test were used to examine the above behavioral dynamic parameters. The dynamic interaction between Residents and Intruders during the study showed substantial alterations in exploratory activity, aggressiveness, defensive behavior, body weight, and thymus mass in stressed animals. N-14 cotreatment has mitigated sociability, exploratory activity, aggressiveness increased social adaptability and defensive behavior. An extensive rise in active forms of defense and submission latency indicates that N-14 has induced antidepressant activity with a psycho-sedative component of action. Serendipitously, we observed the ameliorative capability of N-14 cotreatment to mitigate depressive-behavioral symptoms in intruders.

MicroRNA Cues from Nature: A Roadmap to Decipher and Combat Challenges in Human Health and Disease?

MicroRNAs are small non-coding RNA (18–24 nt long) that fine-tune gene expression at the post-transcriptional level. With the advent of “multi-omics” analysis and sequencing approaches, they have now been implicated in every facet of basic molecular networks, including metabolism, homeostasis, and cell survival to aid cellular machinery in adapting to changing environmental cues. Many animals must endure harsh environmental conditions in nature, including cold/freezing temperatures, oxygen limitation (anoxia/hypoxia), and food or water scarcity, often requiring them to revamp their metabolic organization, frequently on a seasonal or life stage basis. MicroRNAs are important regulatory molecules in such processes, just as they are now well-known to be involved in many human responses to stress or disease. The present review outlines the role of miRNAs in natural animal models of environmental stress and adaptation including torpor/hibernation, anoxia/hypoxia tolerance, and freeze tolerance. We also discuss putative medical applications of advances in miRNA biology including organ preservation for transplant, inflammation, ageing, metabolic disorders (e.g., obesity), mitochondrial dysfunction (mitoMirs) as well as specialized miRNA subgroups respective to low temperature (CryomiRs) and low oxygen (OxymiRs). The review also covers differential regulation of conserved and novel miRNAs involved at cell, tissue, and stress specific levels across multiple species and their roles in survival. Ultimately, the species-specific comparison and conserved miRNA responses seen in evolutionarily disparate animal species can help us to understand the complex miRNA network involved in regulating and reorganizing metabolism to achieve diverse outcomes, not just in nature, but in human health and disease.

BDNF, A Focus to Major Depression

Major depressive disorder is characterized, among other symptoms, by depressed mood and anhedonia associated with a high rate of suicidal ideation. In recent years, research has shown reduced expression of the brain-derived neurotrophic factor (BDNF) in limbic areas of individuals with depression. This reduction of BDNF is reversed by antidepressants in animal models of stress. Stress is one of the main triggers of mood disorders such as depression. Also, administration of BDNF increases the number of serotonergic fibers and serotonergic innervation, indicating an increase of serotonin in the synaptic cleft by this neurotrophin. Thus, BDNF appears to be one of the targets of antidepressant drugs for the increase of monoamines and remission of symptoms of major depression. The purpose of this review was to show the evidence that indicates BDNF as a molecular substrate for vulnerability to depression and the response of this substrate to the antidepressants.

A salience hypothesis of stress in PTSD.

Attention to key features of contexts and things is a necessary tool for all organisms. Detecting these salient features of cues, or simply, salience, can also be affected by exposure to traumatic stress, as has been widely reported in individuals suffering from post-traumatic stress disorder (PTSD). Interestingly, similar observations have been robustly replicated across many animal models of stress as well. By using evidence from such rodent stress paradigms, in the present review, we explore PTSD through the lens of salience processing. In this context, we propose that interaction between the neurotrophin brain-derived neurotrophic factor (BDNF) and glucocorticoids determines the long lasting cellular and behavioural consequences of stress salience. We also describe the dual effect of glucocorticoid therapy in the amelioration of PTSD symptoms. Finally, by integrating in vivo observations at multiple scales of plasticity, we propose a unifying hypothesis that pivots on a crucial role of glucocorticoid signalling in dynamically orchestrating stress salience.