Stressed Animals Research Articles

Piceatannol promotes hepatic and renal AMPK/SIRT1/PGC-1α mitochondrial pathway in rats exposed to reserpine or gamma-radiation.

Human exposure to radio-therapeutic doses of gamma rays can produce late effects, which negatively affect cancer patients’ quality of life, work prospects, and general health. This study was performed to explore the role of Piceatannol (PIC) in the process of “mitochondrial biogenesis” signaling pathway as possible management of disturbances induced in stressed animal model(s) either by gamma-irradiation (IR) or administration of reserpine (RES); as a mitochondrial complex-I inhibitor. PIC (10 mg/kg BW/day; orally) were given to rats for 7 days, after exposure to an acute dose of γ-radiation (6 Gy), or after a single reserpine injection (1 g/kg BW; sc). Compared to reserpine or γ-radiation, PIC has attenuated hepatic and renal mitochondrial oxidative stress denoted by the significant reduction in the content of lipid peroxides and NO with significant induction of SOD, CAT, GSH-PX, and GR activities. PIC has also significantly alleviated the increase of the inflammatory markers, TNF-α and IL-6 and apoptotic markers, cytochrome c, and caspase-3. The decrease of oxidative stress, inflammation, and apoptotic responses were linked to a significant amelioration in mitochondrial biogenesis demonstrated by the increased expression and proteins’ tissue contents of SIRT1/p38-AMPK, PGC-1α signaling pathway. The results are substantiated by the significant amelioration in mitochondrial function verified by the higher levels of ATP content, and complex I activity, besides the improvement of hepatic and renal functions. Additionally, histopathological examinations of hepatic and renal tissues showed that PIC has modulated tissue architecture after reserpine or gamma-radiation-induced tissue damage. Piceatannol improves mitochondrial functions by regulating the oxidant/antioxidant disequilibrium, the inflammatory and apoptotic responses, suggesting its possible use as adjuvant therapy in radio-therapeutic protocols to attenuate hepatic and renal injuries.

A Review of the State of Purinergic Signaling and Psychological Stress

Purinergic signaling is involved in multiple physiological and pathological processes. Psychological stress, as an inharmonious state in response to stressors, is closely related to the function or dysfunction of purinergic signaling. Abnormal expression of ATP interceptors caused by stress leads to psychological stress-related diseases, such as anxiety, depression, post-traumatic stress disorder and schizophrenia. Recent studies demonstrate that a complex network of purinergic signaling (such as ATP, adenosine and P2X2R, P2X3R, P2X4R, P2X7R, A1R, A2AR) plays a key role in psychological stress, but the specific mechanism remains to be further studied. And few studies focus on the application of ATP real-time detecting to psychological stress animal models, so the specific biological role of ATP in the process of stress is still unknown. This review will summarize the relationship between purinergic signaling and psychological stress and propose to apply the duplicate ATP real-time detection technology and purinergic compounds on psychological stress research in order to provide novel potential targets for the treatment of stress-related diseases.

Superior antioxidant and anti-ischemic neuroprotective effects of cerebrolysin in heat stroke following intoxication of engineered metal Ag and Cu nanoparticles: A comparative biochemical and physiological study with other stroke therapies.

Military personnel are often exposed to high environmental heat associated with industrial or ambient abundance of nanoparticles (NPs) affecting brain function. We have shown that engineered metal NPs Ag and Cu exacerbate hyperthermia induced brain pathology. Thus, exploration of novel drug therapy is needed for effective neuroprotection in heat stroke intoxicated with NPs. In this investigation neuroprotective effects of cerebrolysin, a balanced composition of several neurotrophic factors and active peptides fragments exhibiting powerful antioxidant and anti-ischemic effects was examined in heat stroke after NPs intoxication. In addition, its efficacy is compared to currently used drugs in post-stroke therapies in clinics. Thus, levertiracetam, pregabalin, topiramat and valproate were compared in standard doses with cerebrolysin in heat stroke intoxicated with Cu or Ag NPs (50-60nm, 50mg/kg, i.p./day for 7 days). Rats were subjected to 4h heat stress (HS) in a biological oxygen demand incubator at 38°C (Relative Humidity 45-47%; Wind velocity 22.4-25.6cm/s) that resulted in profound increase in oxidants Luminol, Lucigenin, Malondialdehyde and Myeloperoxidase, and a marked decrease in antioxidant Glutathione. At this time severe reductions in the cerebral blood flow (CBF) was seen together with increased blood-brain barrier (BBB) breakdown and brain edema formation. These pathophysiological responses were exacerbated in NPs treated heat-stressed animals. Pretreatment with cerebrolysin (2.5mL/kg, i.v.) once daily for 3 days significantly attenuated the oxidative stress, BBB breakdown and brain edema and improved CBF in the heat stressed group. The other drugs were least effective on brain pathology following heat stroke. However, in NPs treated heat stressed animals 5mL/kg conventional cerebrolysin and 2.5mL/kg nanowired cerebrolysin is needed to attenuate oxidative stress, BBB breakdown, brain edema and to improve CBF. Interestingly, the other drugs even in higher doses used are unable to alter brain pathologies in NPs and heat stress. These observations are the first to demonstrate that cerebrolysin is the most superior antioxidant and anti-ischemic drug in NPs exposed heat stroke, not reported earlier.

Melatonin attenuated the behavioral despair induced by acute neurogenic stress through blockade of N-methyl D-aspartate receptors in mice

It has been well documented that administration of melatonin could reveal antidepressant-like effect in rodents. However, the protective effect of melatonin on stress-induced depression/anxiety and its underlying mechanism is yet to be understood. In this regard, in the current study, acute foot-shock stress (FSS) was used to evaluate the antidepressant-like effect of melatonin on neurogenic stress-induced depression in mice. Behavioral evaluation was done by using the forced swimming test (FST) and Open-field test (OFT). Melatonin, MK-801, and ketamine (NMDA receptor antagonists), and NMDA (NMDA receptor agonist) were used to elucidate any association between melatonin and NMDA pathway in behavioral despair induced by acute-FSS. Applying acute-FSS to mice significantly induced depressant-like behavior in FST without any significant impact on locomotor activity in the OFT. We observed that melatonin (dose-dependently) significantly improved the depressant-like effect of FSS, but it did not impact the locomotion in animals. Acute injection of MK-801 at sub-effective doses (0.01 mg/kg) or ketamine (0.1 mg/kg) potentiated the antidepressant-like effect of a sub-effective dose of melatonin. However, the sub-effective dose of NMDA (30 mg/kg) abolished the protective effect of melatonin on the behavioral profile of stressed animals. Our results could reflect the antidepressant-like effect of melatonin on neurogenic stress-induced depressive behaviors in mice. Also, our results showed that NMDA receptors could be involved in the antidepressant-like effect of melatonin.

Sex-specific effects of social defeat stress on miRNA expression in the anterior BNST

Women are more likely to suffer from stress-related affective disorders than men, but the underlying mechanisms of sex differences remain unclear. Previous works show that microRNA (miRNA) profiles are altered in stressed animals and patients with depression and anxiety disorders. In this study, we investigated how miRNA expression in the anterior bed nucleus of stria terminalis (BNST) was affected by social defeat stress in female and male California mice (Peromyscus californicus). We performed sequencing to identify miRNA transcripts in the whole brain and anterior BNST followed by qPCR analysis to compare miRNA expression between control and stressed animals. The results showed that social defeat stress induced sex-specific miRNA expression changes in the anterior BNST. Let-7a, let-7f and miR-181a-5p were upregulated in stressed female but not male mice. Our study provided evidence that social stress produces distinct molecular responses in the BNST of males and females.

Evaluation of the Effect of Hypericum triquetrifolium Turra on Memory Impairment Induced by Chronic Psychosocial Stress in Rats: Role of BDNF.

BackgroundChronic psychosocial stress impairs memory function and leads to a depression-like phenotype induced by a persistent status of oxidative stress. Hypericum perforatum L. (St. John’s wort) is widely used to relieve symptoms of anxiety and depression; however, its long-term use is associated with adverse effects. Hypericum triquetrifolium Turra is closely related to H. perforatum. Both plants belong to Hypericaceae family and share many biologically active compounds. Previous work by our group showed that methanolic extracts of H. triquetrifolium have potent antioxidant activity as well as high hypericin content, a component that proved to have stress-relieving and antidepressant effects by other studies. Therefore, we hypothesized that H. triquetrifolium would reduce stress-induced cognitive impairment in a rat model of chronic stress.ObjectiveTo determine whether chronic treatment with H. triquetrifolium protects against stress-associated memory deficits and to investigate a possible mechanism.MethodsThe radial arm water maze (RAWM) was used to test learning and memory in rats exposed to daily stress using the resident–intruder paradigm. Stressed and unstressed rats received chronic H. triquetrifolium or vehicle. We also measured levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, cortex and cerebellum.ResultsNeither chronic stress nor chronic H. triquetrifolium administration affected performance during acquisition. However, memory tests in the RAWM showed that chronic stress impaired different post-encoding memory stages. H. triquetrifolium prevented this impairment. Furthermore, hippocampal BDNF levels were markedly lower in stressed animals than in unstressed animals, and chronic administration of H triquetrifolium chronic administration protected against this reduction. No significant difference was observed in the effects of chronic stress and/or H. triquetrifolium treatment on BDNF levels in the cerebellum and cortex.ConclusionH. triquetrifolium extract can oppose stress-associated hippocampus-dependent memory deficits in a mechanism that may involve BDNF in the hippocampus.

English

The study aims to show the possible anxiolytic and antidepressant-like properties of an oral lavender’s flower aqueous extract (LAE) in chronic mild stress (CMS) model of rats. Test and control rats received LAE (200 or 400 mg/ kg) and distilled water respectively. Tests of Sucrose preference (SP), elevated plus maze (EPM), and open field (OFT) were used to evaluate rats’ behavioral changes.  The percentage of SP in the CMS group was 2.6 times less than that of the unstressed group (p<0.05). However, administration of LAE (200 and 400 mg / kg) increased SP of CMS rats by 2.0 and 3.01 times respectively in comparison to those of the stressed animals. EPM analysis revealed that 5-week CMS exposure significantly reduced the number of entries in open arm (0.8 times) as compared to unstressed rats (6.6 times). LAE (200 and 400 mg / kg) reversed CMS by increasing both the total time spent (1.73 and 1.23% respectively) and the number of entries in open arm (5 and 5.7 times respectively) compared to those related to unstressed group (p< 0.05). CMS decreased the number of entries and time spent in the central zone of OFT. Administration of LAE (200 and 400 mg/ kg) to stressed rats enhanced the total distance traveled respectively by 3.30 and 2.65% than the control rats. Taken together, oral lavender aqueous extracts showed ameliorating effects on the depression and anxiety-related behaviors in rats. Key words: Depression, lavender, chronic mild stress, anxiety, aqueous extract.

Phenotypic and genomic analyses of agonistic interactions in laying hen lines divergently selected for feather pecking

In poultry, aggressive pecking and threatening are normal agonistic behavior patterns which serve to establish a social hierarchy. As agonistic behavior is a stressor for animals, its excessive occurrence is undesired in layer flocks. Feather pecking is a longstanding serious problem in layer flocks and its relationship to agonistic behavior is still not clear. Therefore, phenotypic and genomic analyses of the agonistic and feather pecking behavior of two laying hen lines divergently selected for high and low feather pecking were conducted. The hens were phenotyped for the active traits aggressive pecks delivered (APD)11Aggressive pecks delivered (APD), threats delivered (TD)22Threats delivered (TD), feather pecks delivered (FPD)33Feather pecks delivered (FPD) and the passive traits aggressive pecks received (APR)44Aggressive pecks received (APR), threats received (TR)55Threats received (TR) and feather pecks received (FPR)66Feather pecks received (FPR). Indices were built by subtracting the passive traits from the respective active traits to obtain the aggression index, the threat index, and the feather pecking index. As all three behavior patterns in their excessive manifestations are undesired, the index-traits Activity and Passivity were also defined by combining each the active and passive traits. The results showed that FPD is significantly positive correlated with APD and TD in both lines, but with higher coefficients in the high feather pecking line. The average amount of FPR in both lines is nearly the same and no correlation was found between FPR and FPD, APD or TD in any of the lines. The active traits and the feather pecking index showed medium heritabilities, whereas the heritability was negligibly small for the other traits. GWAS revealed four nominal significant (p ≤ 5*10−5) SNPs for APD on chromosome 6, the same four and three additional SNPs on chromosome 8 for Activity and three SNPs on chromosome 1 for the feather pecking index. It is concluded, that selection on high feather pecking leads to an increase of agonistic behavior. The correlation probably depends on the phase of establishing the social hierarchy in which the hens in a newly formed group are at the time of observation, and might disappear, after a stable ranking is established. The reception of feather pecking is similar in both lines. GWAS revealed that TD, APD, Activity and the feather pecking index seem to be typical quantitative traits with associated regions for the latter three which have slightly greater effects on these traits than other regions in the genome.

DNA Methyltransferase 3A Is Involved in the Sustained Effects of Chronic Stress on Synaptic Functions and Behaviors

Abstract Emerging evidence suggests that epigenetic mechanisms regulate aberrant gene transcription in stress-associated mental disorders. However, it remains to be elucidated about the role of DNA methylation and its catalyzing enzymes, DNA methyltransferases (DNMTs), in this process. Here, we found that male rats exposed to chronic (2-week) unpredictable stress exhibited a substantial reduction of Dnmt3a after stress cessation in the prefrontal cortex (PFC), a key target region of stress. Treatment of unstressed control rats with DNMT inhibitors recapitulated the effect of chronic unpredictable stress on decreased AMPAR expression and function in PFC. In contrast, overexpression of Dnmt3a in PFC of stressed animals prevented the loss of glutamatergic responses. Moreover, the stress-induced behavioral abnormalities, including the impaired recognition memory, heightened aggression, and hyperlocomotion, were partially attenuated by Dnmt3a expression in PFC of stressed animals. Finally, we found that there were genome-wide DNA methylation changes and transcriptome alterations in PFC of stressed rats, both of which were enriched at several neural pathways, including glutamatergic synapse and microtubule-associated protein kinase signaling. These results have therefore recognized the potential role of DNA epigenetic modification in stress-induced disturbance of synaptic functions and cognitive and emotional processes.

Establishing models of corticosteroid patterns during the life history of killer whales (Orcinus orca) under human care

The use of corticosteroids and their metabolites as a physiologic measure of stress in wildlife species is increasing in both in and ex situ populations. However, factors such as season, circadian rhythm, sex and age are also known to influence corticosteroid production in wildlife. Our objective was to evaluate the influence of these variables on serum cortisol, corticosterone, aldosterone and their fecal metabolites in zoo-based killer whales (Orcinus orca). For evaluation of season, sex and age, we examined 30 animals (21 females, 9 males), and for circadian rhythm, we studied 18 animals (10 females, 8 males). Season did not influence corticosteroids (P ≥ 0.19). Circadian rhythm influenced all corticosteroids (P ≤ 0.012). Serum cortisol and corticosterone were highest in the morning and lower by mid-day and evening. Serum aldosterone was lowest during mid-day and highest in the evening. Excreted corticosteroid metabolites were higher in the morning and mid-day compared to evening (P ≤ 0.002). Serum cortisol was higher in males than females (P = 0.011). The inverse was observed for fecal corticosterone metabolites (P = 0.03). Serum corticosterone increased with age in all animals (P = 0.002), but serum cortisol increased with age in males only (P < 0.001). Finally, combining previously published data and these data reported herein, we developed models of corticosteroid patterns for zoo-based killer whales during life history events, including circadian variation, pregnancy and acute stress that may serve as a guide for evaluating stress physiology and animal welfare in this species.

Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice.

Early life stress (ELS) is considered a risk factor for the development of psychiatric conditions, including depression and anxiety disorder. Individuals that live in adverse environments are usually exposed to multiple stressors simultaneously, such as maternal neglect, maltreatment, and limited resources. Nevertheless, most pre-clinical ELS models are designed to explore the impact of these events separately. For this reason, this study aims to investigate the effects of a combined model of ELS on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis related targets. From PND 2 to PND 15 BALB/cJ mice were exposed simultaneously to maternal separation (MS; 3 h per day) and limited bedding (LB; ELS group) or left undisturbed (CT group). Maternal behavior was recorded in intercalated days, from PND 1 to PND 9. Male offspring were tested for anxiety-like behavior from PND 53 to PND 55 in the open field test (OF), elevated plus-maze (EPM), and light/dark test (LD). After behavioral testing, animals were euthanized, and glucocorticoid receptor (Nr3c1), corticotrophin-releasing hormone (Crh), and its receptor type 1 (Crhr1) gene expression in the hypothalamus were measured. Moreover, plasma corticosterone levels were analyzed. We observed that ELS dams presented altered quality of maternal care, characterized by a decrease in arched-back nursing, and an increase in passive nursing. Stressed dams also showed an increase in the number of exits from the nest when compared to CT dams. Furthermore, ELS animals showed increased anxiety-like behavior in the OF, EPM, and LD. Regarding gene expression, we identified an increase in hypothalamus Crh levels of ELS group when compared to CT animals, while no differences in Nr3c1 and Crhr1 expression were observed. Finally, stressed animals showed decreased levels of plasma corticosterone when compared to the CT group. In conclusion, we observed an alteration in maternal behavior in ELS dams. Later in life, animals exposed to the combined model of ELS showed increased levels of anxiety-like behavior. Moreover, the central and peripheral HPA measures observed could indicate a dysregulation in HPA function provoked by ELS exposure.

Adaptogenic effects of curcumin on depression induced by moderate and unpredictable chronic stress in mice

Curcumin has been investigated for the prevention and treatment of diseases due to its anti-oxidant, anti-inflammatory, immunomodulatory, and neuroprotective actions. This current study evaluated the adaptogenic effects of a subchronic oral administration of curcumin to Swiss mice that were submitted to a chronic unpredictable mild stress (CUMS) model of depression. Four groups of mice (vehicle control, CO; curcumin control, COC; CUMS + vehicle, CUMS; CUMS + curcumin, CUMSC) were evaluated for the biochemical parameters. The CUMS model caused depressive-like and anxiety-like behavior in the animals when they were viewed in the Forced Swimming Test and in the Elevated Plus Maze Test. The treatments with curcumin prevented the depressive-like behavior in the Forced Swimming Test and they had anxiolytic effects on the non-stressed animals. This was confirmed by the Elevated Plus Maze Test. Curcumin showed antioxidant effects (IC50 of 38.86 ± 1.78 μg/mL) in the in vitro DPPH (2,2-diphenyl-1-picryl-hydrozole) test. The compound also showed antioxidant effects in vivo, increasing the catalase (CAT) levels in the brains of the stressed animals. The biochemical analyses did not reveal potential renal and hepatic damage. Together, these results have demonstrated the antidepressant and antioxidant effects of curcumin, highlighting in this mice model, the compound’s novel adaptogenic potential.

Fish and hyperoxia—From cardiorespiratory and biochemical adjustments to aquaculture and ecophysiology implications

AbstractHyperoxia occurs when water oxygen (O2) levels exceed normal atmospheric pressure (i.e., &gt;100% air saturation). Fish can experience hyperoxia in shallow environments due to photosynthesis or in aquaculture through O2 supplementation. This review provides a comprehensive synthesis of the effects of hyperoxia on fish, spanning influences on cardiorespiratory function, acid‐base balance, oxidative stress and whole animal performance (e.g., thermal tolerance and growth). Fish hypoventilate in hyperoxia, but arterial and venous blood oxygenation increases in spite of reduced convection. Persistently high levels of blood oxygenation in hyperoxia do not commonly result in reduced blood O2 carrying capacity, but assessments in undisturbed fish are required to clarify this. Hypoventilation also causes the retention of carbon dioxide, hence respiratory acidosis. Another consequence of hyperoxia is increased levels of oxidative stress and concomitant changes to antioxidant defence systems. Despite these changes, however, the bulk of evidence shows no effect of hyperoxia on growth. Hyperoxia does impact the aerobic metabolic rate of fish with either no effect or elevated resting metabolic rate and substantial increases in maximum metabolic rate. There is also evidence that hyperoxia increases aerobic capacity improves cardiac performance and mitigates anaerobic stress during acute warming. Along with improved upper thermal tolerance in some species, these findings collectively suggest that hyperoxia might provide fish a metabolic refuge during acute warming. Since hyperoxia occurs in shallow aquatic habitats, further research establishing the ecophysiological implications of concomitant heat stress and hyperoxia is pertinent, particularly with a changing climate.

Zinc/Iron oxide nanocomposites: Green synthesis, characterization, and evaluation of their effects on anxiety in rats exposed to noise stress.

In the modern lifestyle, environmental stresses have substantially influenced human life. Evidence indicates that noise exposure can lead to anxiety-like behaviors. In recent years, advances in nanotechnology have favorably impacted industrial productions. In the present study, we aimed to evaluate the effect of Zinc/Iron oxide nanocomposites on anxiety-like behavior. Using gelatin, Zinc/Iron oxide nanocomposites were synthesized by the sol-gel modified method. Four groups of rats were exposed to sound stress for 12 days. Three groups received 1.25, 2.5, and 5 mg/kg of Zinc/Iron oxide nanocomposites before the noise stress. Also, three control animals received the same doses of the nanocomposites. One group of the stressed (ST) and control (CO) rats received saline. The animals were introduced to the elevated plus maze (EPM) for the assessment of anxiety. Entry to closed arms, duration of stay in open arms were considered for data analysis. We observed a significant difference between the behavior of the CO and ST animals so that the latter group showed more anxiety compared to the former one. Concerning the effect of Zinc/Iron oxide nanocomposites, the data analysis confirmed the positive effect of the dose of 2.5 mg/kg where the stressed animals treated with this dose of the nanocomposites considerably improved their normal performance in the EPM.

The preclinical studies of the stress-protective activity of “Tonus-aktiv” homeopathic granules

Aim. To perform the preclinical studies of the stress-protective activity of a new “Tonus-Aktiv” homeopathic medicinal product.Materials and methods. The stress-protective effect of the “Tonus-Aktiv” homeopathic medicinal product (MP) and the reference drug – “Stress-gran” homeopathic granules were studied on the model of neuromuscular tension by Selye. The stress-protective effect of the drugs was assessed by the conventional methods described in the scientific literature and the corresponding current instructional guidelines. All factual material was processed by variational statistics methods using parametric (Newman-Keuls test) and non-parametric methods of analysis (Kruskal-Wallis, Mann-Whitney).Results and discussion. It was found that “Tonus-Aktiv” had a pronounced gastro-protective effect, reducing the area of ulcers by almost 3 times, having a statistically significant antioxidant effect, reducing the level of TBA (thiobarbituric acid) active products in the liver homogenate. It did not have a normalizing effect on the protein metabolism, but it did contribute to enhancing energy-supplying metabolic processes: aerobic glycolysis indicated by a reliable increase of the pyruvic acid level in the blood serum, and lipolysis, as evidenced by a significantly higher level of the total blood lipids. “Tonus-Aktiv” showed a pronounced antioxidant activity: it reduced the TBA level of active products in the liver homogenate. At the same time, the level of endogenous antioxidant of reduced glutathione was observed to be lower than in the stressed animals against the background of the “Tonus-Aktiv” application. It indicates the physiological nature of the stress protective activity of the drug.Conclusions. A moderate stress-protective activity of “Tonus-Aktiv” homeopathic granules can be observed; it is caused by antioxidant properties, as well as a probable activating effect on the hypothalamic-pituitary-adrenal system, which may be manifested by the protective action.

Detection of changes in the circadian rhythm of cattle in relation to disease, stress, and reproductive events.

Disease and stress can disrupt the circadian rhythm of activity in animals. Sensor technologies can automatically detect variations in daily activity, but it remains difficult to detect exactly when the circadian rhythm disruption starts. Here we report a mathematical Fourier-Based Approximation with Thresholding (FBAT) method designed to detect changes in the circadian activity rhythm of cows whatever the cause of change (typically disease, stress, oestrus). We used data from an indoor positioning system that provides the time per hour spent by each cow resting, in alleys, or eating. We calculated the hourly activity level of each cow by attributing a weight to each activity. We considered 36-h time series and used Fourier transform to model the variations in activity during the first and last 24h of these 36-h series. We then compared the Euclidian distance between the two models against a given threshold above which we considered that rhythm had changed. We tested the method on four datasets (giving a cumulative total of ~120000 cow*days) that included disease episodes (acidosis, lameness, mastitis or other infectious diseases), reproductive events (oestrus or calving) and external stimuli that can stress animals (e.g. relocation). The method obtained over 80% recall of normal days and detected 95% of abnormal rhythms due to health or reproductive events. FBAT could be implemented in precision livestock farming system monitoring tools to alert caretakers to individual animals needing specific care. The FBAT method also has the potential to detect anomalies in humans to guide healthcare intervention or in wild animals to detect disturbances. We anticipate that chronobiological studies could apply FBAT to help relate circadian rhythm anomalies to specific events.

Stress-induced increased expression of TLR2, TLR3, and TLR4 genes in hypothalamic tissue

The aim of this work was to study the expression of Toll-like receptors (TLRs) genes in the hypothalamic structures of the brain, after the application of acute stressful effects. A hypothesis has been put forward about Toll-like receptors as a key link in the mechanisms of the implementation of a stress reaction, including at the level of the central nervous system (CNS). The important role of TLR in the pathogenesis of stress-mediated diseases of the central nervous system is assumed. The expression of TLR2, TLR3, and TLR4 genes in rat hypothalamus was studied for after 3 hours after the application of acute emotional-physical stress. A reliable increase in the level of gene expression of all three receptors at the mRNA level in stressed animals was established compared with the control. The obtained experimental data indicate the activation of the system of Toll-like receptors at the level of the central nervous system under stress. The activation of several receptors of the TLR family with different specificities in the absence of an increase in microbial load, including at the level of pathogen-associated molecular factors (PAMP), may also indicate the likely significant role of endogenous TLR ligands in the described processes.

Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling

Stress and lipopolysaccharide (LPS) animal models are used for screening antidepressants and anxiolytic drugs. However, the lacunae for their combination (Restraint stress; RS and LPS) impacting inflammation, apoptosis and antioxidant signaling have not been explored. The present study investigated RS + LPS-induced neurobehavioral and neurochemical anomalies in hippocampus (HIP) and frontal cortex (FC) of mice. Furthermore, citrus-derived flavanone glycoside (Hesperidin; HSP) neuroprotective ability was also confirmed in this model. Male Balb/c mice were given RS (for 28 days) and LPS (single dose, 0.83 mg/kg, i.p.) on 28th day. RS + LPS challenge caused neurobehavioral deficits in mice as evaluated over elevated plus maze (EPM), open field test (OFT), light-dark box test, tail suspension test (TST), forced swim test (FST), sucrose preference test (SPT). Moreover, RS + LPS caused alteration via enhanced oxido-nitrosative stress, proinflammatory cytokines level (serum, HIP, FC), lower antioxidants (GSH, SOD, CAT), increased IBA-1, GFAP, TLR4/NF-κB, p38MAPK/JNK while decreased Nrf2/BDNF/HO-1 expression in HIP and FC of mice. The 21 days (8–28th day), HSP (50 and 100 mg/kg, p.o.) treatment significantly alleviated the anxiety and depressive-like behavior and reversed neurochemical, histopathological changes. HSP exerted the neuroprotective effect via its anti-inflammatory, anti-apoptotic, antioxidant and neurogenesis potential in treating psychiatric illness alone or associated with other diseases.

Вплив стресу та фітоестрогенізації у неонатальний період на фертильність статевозрілих самців щурів

In the paper the significance of milk-feeding period for the formation of male reproductive health is experimentally shown. It has been found that the use of emotional stress and excessive phytoestrogenization, both separately and together, in male rats during breastfeeding leads to certain disorders of the reproductive system in adulthood. Modeled emotional stress or phytoestergenization on the principle of imprinting caused hyperostrogeny, androgen deficiency, changes in the ratio of androgenization/estrogenization in adulthood. The applied factors led to impaired spermatogenesis, inhibition of sexual activity, and decreased reproductive potential. In the stressed animals, the decrease in androgens was such that the testosterone levels did not differ from intact females. In the case of joint application of the factors in the suckling period, in adult male rats there were no clinically significant changes in the sperm count. The concentration of sex hormones corresponded to the physiological norm, sexual behavior was characterized by slightly differentiated changes. However, a 2.5-fold decrease in their fertility (or potential number of offspring) was critical and largest among all study groups. The latter indicates impaired spermatogenesis and the formation of defective sperm, that is, the problem of the parental genome, possibly epigenetic in nature.

Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder.

Hexobarbital sleep test (HST) was performed in male Wistar rats (hexobarbital 60 mg/kg, i.p.) 30 days prior to stress exposure. Based on the duration of hexobarbital-induced sleep, rats were divided into two groups, animals with high intensity (fast metabolizers (FM), sleep duration <15 min) or low intensity of hexobarbital metabolism (slow metabolizers (SM), sleep duration ≥15 min). The SM and FM groups were then divided into two subgroups: unstressed and stressed groups. The stressed subgroups were exposed to predator scent stress for 10 days followed by 15 days of rest. SM and FM rats from the unstressed group exhibited different behavioral and endocrinological patterns. SM showed greater anxiety and higher corticosterone levels. In stressed animals, anxiety-like posttraumatic stress disorder (PTSD) behavior was aggravated only in SM. Corticosterone levels in the stressed FM, PTSD-resistant rats, were lower than in unstressed SM. Thus, HST was able to predict the susceptibility or resistance to experimental PTSD, which was consistent with the changes in glucocorticoid metabolism.