Stressed Animals Research Articles

Soluble amyloid-β dimers are resistant to amyloid-β prion conversion in vivo suggesting antiprion properties.

According to the instructions for authors, short communications should be published without abstract.

Correlation between circulating cortisol and indicators of stress and oxidant stress during the preslaughter operations in camels

In livestock, pre-slaughter stress begins at the farm or market, continues during transport and upon arrival at the slaughterhouse, ending at slaughter. In this investigation, a survey was conducted in the slaughterhouse of Casablanca in Morocco to record the duration of the preslaughter operations and the frequency of urination in camels. Two groups of camels were constituted, the least stressed animals (Group I, n= 12) and the most stressed animals (Group II, n= 12). Group I animals had a waiting time before loading ≤ 24 h, a loading time ≤ 15 min, an unloading time ≤ 5 min, a water and food deprivation time before slaughter ≤ 24 h, a duration of accompaniment to the slaughter room ≤ 11 min and a frequency of urination during this accompaniment < 3 times. Those in group II had higher duration and frequency values for the same parameters. In addition, serum stress [cortisol (COR)], oxidant stress biomarkers [malondialdehyde (MDA)] and activities of catalase (CAT) and superoxide dismutase (SOD) were analyzed in both groups, and correlations between these biomarkers and the durations of various preslaughter operations and the frequency of urination were established. The most stressed camels (G II) showed high serum concentrations of COR and MDA, and low CAT and SOD activities by comparison to the less stressed camels (G I) (P<0.05). Significant correlations were recorded between COR, MDA, CAT and SOD, and the durations of various preslaughter operations, and between COR and the frequency of urination.

IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice

Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model. Female and male C57Bl/6J wild-type (WT) and IL-1αβ-deficient (knock-out: IL-1 KO) mice were exposed to 6 h of immobilization/day for 4 weeks. Mechanonociception, cold tolerance, behavioral alterations, relative thymus/adrenal gland weights, microglia ionized calcium-binding adaptor molecule 1 (IBA1) and astrocyte glial fibrillary acidic protein (GFAP) integrated density, number and morphological transformation in pain-related brain regions were determined. CRS induced 15-20% mechanical hyperalgesia after 2 weeks in WT mice in both sexes, which was significantly reduced in female but not in male IL-1 KOs. Increased IBA1+ integrated density in the central nucleus of amygdala, primary somatosensory cortex hind limb representation part, hippocampus cornu ammonis area 3 (CA3) and periaqueductal gray matter (PAG) was present, accompanied by a cell number increase in IBA1+ microglia in stressed female WTs but not in IL-1 KOs. CRS induced morphological changes of GFAP+ astrocytes in WT but not in KO mice. Stress evoked cold hypersensitivity in the stressed animals. Anxiety and depression-like behaviors, thymus and adrenal gland weight changes were detectable in all groups after 2 but not 4 weeks of CRS due to adaptation. Thus, IL-1 mediates chronic stress-induced hyperalgesia in female mice, without other major behavioral alterations, suggesting the analgesic potentials of IL-1 in blocking drugs in stress-related pain syndromes.

T-Cell Repertoire Analysis in the Conjunctiva of Murine Dry Eye Model.

Dry eye is closely related to the activation and proliferation of immune cells, especially T cells. However, the determination of the preferential T-cell clonotypes is technically challenging. This study aimed to investigate the characterization of T-cell receptor (TCR) repertoire in the conjunctiva during dry eye. A desiccating stress animal model was established using C57/BL6 mice (8-10 weeks, female). After 7 days of stress stimulation, the slit-lamp image and Oregon-green-dextran staining were used to evaluate the ocular surface injury. Periodic acid-Schiff staining was used to measure the number of goblet cells. Flow cytometry was used to detect the activation and proliferation of T cells in the conjunctiva and cervical lymph nodes. Next-generation sequencing was used to detect the αβ TCR repertoire of the conjunctiva. The αβ TCR diversity increased significantly in the dry eye group, including the higher CDR3 amino acid length, marked gene usage on TCR V and J gene segments, extensive V(D)J recombination, and distinct CDR3 aa motifs. More important, several T-cell clonotypes were uniquely identified in dry eye. Furthermore, these perturbed rearrangements were reversed after glucocorticoid administration. A comprehensive analysis of the αβ TCR repertoire in the conjunctiva of the dry eye mouse model was performed. Data in this study contributed significantly to the research on dry eye pathogenesis by demonstrating the TCR gene distribution and disease-specific TCR signatures. This study further provided some potential predictive T-cell biomarkers for future studies.

The expression of agmatinase manipulates the affective state of rats subjected to chronic restraint stress

Agmatine is an endogenous polyamine produced from l-arginine and degraded by agmatinase (AGMAT). Studies in humans and animals have shown that agmatine has neuroprotective, anxiolytic, and antidepressant-like actions. However, little is known about the role of AGMAT in the action of agmatine or in the pathophysiology of psychiatric disorders. Therefore, this study aimed to investigate the role of AGMAT in the pathophysiology of MDD. In this study, we observed that AGMAT expression increased in the ventral hippocampus rather than in the medial prefrontal cortex in the chronic restraint stress (CRS) animal model of depression. Furthermore, we found that AGMAT overexpression in the ventral hippocampus elicited depressive- and anxiety-like behaviors, whereas knockdown of AGMAT exhibited antidepressant and anxiolytic effects in CRS animals. Field and whole-cell recordings of hippocampal CA1 revealed that AGMAT blockage increased Schaffer collateral-CA1 excitatory synaptic transmission, which was expressed both pre- and post-synaptically and was probably due to the inhibition of AGMAT-expressing local interneurons. Therefore, our results suggest that dysregulation of AGMAT is involved in the pathophysiology of depression and is a potential target for designing more effective antidepressants with fewer adverse effects to offer a better therapy for depression.

Targeting the Endoplasmic Reticulum Stress-Linked PERK/GRP78/CHOP Pathway with Magnesium Sulfate Attenuates Chronic-Restraint-Stress-Induced Depression-like Neuropathology in Rats.

Magnesium sulfate has demonstrated marked neuroprotection in eclampsia, hypoxia, stroke, and post-traumatic brain injury rodent models. However, its potential impact against chronic-restraint-stress (CRS)-induced depression-like neuropathology and associated alterations in endoplasmic reticulum (ER) stress have not been adequately examined. The present study aimed to investigate the neuroprotective potential of magnesium sulfate in a rat model of CRS-triggered depression-like behavioral disturbance and the underlying molecular mechanisms. Herein, CRS was induced by placing rats into restraining tubes for 6 h/day for 21 days and the animals were intraperitoneally injected with magnesium sulfate (100 mg/kg/day) during the study period. After stress cessation, the depression-like behavior was examined by the open-field test, sucrose preference test, and forced swimming test. The present data demonstrated that CRS triggered typical depression-like behavioral changes which were confirmed by the Z-normalization scores. Mechanistically, serum circulating corticosterone levels spiked, and the hippocampi of CRS-exposed animals demonstrated a significant decline in serotonin, norepinephrine, and dopamine neurotransmitters. At the molecular level, the hippocampal pro-inflammatory TNF-alpha and IL-1β cytokines and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-HG) increased in stressed animals. In tandem, enhancement of hippocampal ER stress was evidenced by the activation of iNOS/PERK/GRP78/CHOP axis seen by increased protein expression of iNOS, PERK, GRP78, and CHOP signal proteins in the hippocampi of stressed rats. Interestingly, magnesium sulfate administration attenuated the depression-like behavioral outcomes and the histopathological changes in the brain hippocampi. These favorable actions were driven by magnesium sulfate's counteraction of corticosterone spike, and hippocampal neurotransmitter decline, alongside the attenuation of neuroinflammation, pro-oxidation, and ER stress. In conclusion, the current results suggest the promising neuroprotective/antidepressant actions of magnesium sulfate in CRS by dampening inflammation, ER stress, and the associated PERK/GRP78/CHOP pathway.

Environmental Enrichment Promotes Transgenerational Programming of Uterine Inflammatory and Stress Markers Comparable to Gestational Chronic Variable Stress

Prenatal maternal stress is linked to adverse pregnancy and infant outcomes, including shortened gestation lengths, low birth weights, cardio-metabolic dysfunction, and cognitive and behavioural problems. Stress disrupts the homeostatic milieu of pregnancy by altering inflammatory and neuroendocrine mediators. These stress-induced phenotypic changes can be passed on to the offspring epigenetically. We investigated the effects of gestational chronic variable stress (CVS) in rats using restraint and social isolation stress in the parental F0 generation and its transgenerational transmission across three generations of female offspring (F1-F3). A subset of F1 rats was housed in an enriched environment (EE) to mitigate the adverse effects of CVS. We found that CVS is transmitted across generations and induces inflammatory changes in the uterus. CVS did not alter any gestational lengths or birth weights. However, inflammatory and endocrine markers changed in the uterine tissues of stressed mothers and their offspring, suggesting that stress is transgenerationally transmitted. The F2 offspring reared in EE had increased birth weights, but their uterine gene expression patterns remained comparable to those of stressed animals. Thus, ancestral CVS induced changes transgenerationally in fetal programming of uterine stress markers over three generations of offspring, and EE housing did not mitigate these effects.

Effect of developmental stress on the in vivo neuronal circuits related to excitation-inhibition balance and mood in adulthood.

Traumatic events in early life have a deleterious effect on the development of normal brain developments, which may be a cause of various psychiatric disorders in adulthood. Most prior studies focused on molecular biological aspects, and research on functional changes in neural circuits is still limited. We aimed to elucidate the effect of early life stress on in vivo excitation-inhibition and serotonergic neurotransmission in the adulthood using non-invasive functional molecular imaging (positron emission tomography, PET). To compare the effect of stress intensity, early life stress animal models were divided into single trauma (MS) and double trauma groups (MRS). MS was derived from maternal separation, whereas MRS was derived from maternal separation and restraint stress after birth. And to evaluate the stress vulnerability on the sex, we used male and female rats. The MRS group showed greater weight loss and more severe depressive/anxiety-like behaviors than the MS and control groups. Corticosterone levels in MRS showed a greater extent of decline than in the MS group; however, there was no significant difference in the change of T3 and T4 between MS and MRS. In the PET, the stress exposure groups showed lower brain uptake for GABAergic, glutamatergic, and serotonergic systems compared with the control group. The excitatory/inhibitory balance, which was derived by dividing glutamate brain uptake into GABAergic uptake, increased as stress intensity increased. Neuronal degeneration in the stress exposure groups was confirmed by immunohistochemistry. In the sex comparison, female showed the greater changes of body weight, corticosterone level, depressive/anxiety-like behavior, and neurotransmission systems than those in male. Taken together, we demonstrated that developmental stress induces dysfunction of neurotransmission in vivo, and that females are more vulnerable to stress than males.

The Political Salience of Animal Protection in the Netherlands (2012–2021) and Belgium (2010–2019): What do Dutch and Belgian Political Parties Pledge on Animal Welfare and Wildlife Conservation?

The Netherlands and Belgium are European Union (EU) states with a shared border and cultural similarities. Article 13 of the EU Treaty of Lisbon recognises animals as sentient beings. EU laws protect animal welfare and conservation, and member states can implement more stringent legislation. Political salience refers to the extent to which citizens are concerned about political issues. Issue salience can be measured by assessing references to animal protection in party political manifestos. This research analyses the political salience of animal protection in the Netherlands and Belgium. It analyses over 2600 statements on animal protection in Dutch (2012–2021) and Belgian (2010–2019) party manifestos across three consecutive national elections. Quantitative analysis reveals that in both the Netherlands and Belgium, animal protection became more salient during successive elections, with the total number of positive statements increasing and the total number of negative statements decreasing. Farmed animal welfare and wildlife/biodiversity were the most salient issues, although the focus in countries and regions differed. Dutch parties and those in the Walloon region of Belgium focused on farmed animal health and unnecessary suffering; Flemish parties stressed intensive agriculture and animal welfare. In Belgium, wildlife/biodiversity statements stressed the protection of local species; Dutch statements were strongly linked to agriculture. In both the Netherlands and Belgium, left-wing parties had more progressive policy statements, whilst right-wing parties prioritised economic prosperity over animal protection. This research provides the first academic analysis of animal protection policies in political manifestos in the Netherlands and Belgium.

Influence of Semax on the Level of Pro- and Anti-Inflammatory Cytokines in Conditions of "Social" Stress

Introduction: This study was devoted to the experimental study of the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) in conditions of "social" stress Aim of the study: to study the effect of Semax on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) under conditions of “social” stress. Materials and methods: White nonlinear rats (males, 6–8 months of age) were used as experimental animals. The animals were divided into groups: 1 – the control group (n=10); 2 – animals exposed to "social" stress (20 days) (n=10 aggressors/10 victims); 3 – rats exposed to "social" stress and receiving Semax intraperitoneally at a dose of 100 μg / kg / day (20 days) (n=10 aggressors/10 victims). Sensory contact was chosen as an experimental model of "social" stress. The level of cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) was determined by the method of enzyme-linked immunosorbent assay. Results: Currently, within the framework of the development of a direction to study the functioning of the unified cytokine network of the body, there is a need for a detailed analysis of changes in the production of individual cytokines during various pathophysiological reactions, including stressful effects. The experimental "social" stress is accompanied by an increase in the production of IL-1β, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of cytokines of the family of proinflammatory interleukins and various growth factors. It was previously thought that inflammation and the immune response are the only factors capable of causing the production of most cytokines. In recent years, scientific works have appeared in which stress occupies an important place among the inducers of cytokine production. This fact has been confirmed by our experiments. Experimental "social" stress is accompanied by changes in the production of IL-1β, IL-4, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of proinflammatory cytokines and growth factors. Conclusion: Evaluation of the effect of Semax on the level of cytokines under conditions of "social" stress showed that the effect of Semax is aimed at restoring the level of the studied cytokines in the group of stressed animals.

Phytochemicals That Act on Synaptic Plasticity as Potential Prophylaxis against Stress-Induced Depressive Disorder.

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.

Male Stressed Mice Having Behavioral Control Exhibit Escalations in Dorsal Dentate Adult-Born Neurons and Spatial Memory.

An escapable (ES)/inescapable stress (IS) paradigm was used to study whether behavioral control and repeated footshock stressors may affect adult neurogenesis and related cognitive function. Male stressed mice having behavioral control (ES) had a short-term escalation in dorsal dentate gyrus (DG) neurogenesis, while similarly stressed mice having no such control had unaltered neurogenesis as compared to control mice receiving no stressors. Paradoxically, ES and IS mice had comparable stress-induced corticosterone elevations throughout the stress regimen. Appetitive operant conditioning and forced running procedures were used to model learning and exercise effects in this escapable/inescapable paradigm. Further, conditioning and running procedures did not seem to affect the mice's corticosterone or short-term neurogenesis. ES and IS mice did not show noticeable long-term changes in their dorsal DG neurogenesis, gliogenesis, local neuronal density, apoptosis, autophagic flux, or heterotypic stress responses. ES mice were found to have a greater number of previously labeled and functionally integrated DG neurons as compared to IS and control mice 6 weeks after the conclusion of the stressor regimen. Likewise, ES mice outperformed IS and non-stressed control mice for the first two, but not the remaining two, trials in the object location task. Compared to non-stressed controls, temozolomide-treated ES and IS mice having a lower number of dorsal DG 6-week-old neurons display poor performance in their object location working memory. These results, taken together, prompt us to conclude that repeated stressors, albeit their corticosterone secretion-stimulating effect, do not necessary affect adult dorsal DG neurogenesis. Moreover, stressed animals having behavioral control may display adult neurogenesis escalation in the dorsal DG. Furthermore, the number of 6-week-old and functionally-integrated neurons in the dorsal DG seems to confer the quality of spatial location working memory. Finally, these 6-week-old, adult-born neurons seem to contribute spatial location memory in a use-dependent manner.

Acute Stress-Induced Changes in the Lipid Composition of Cow's Milk in Healthy and Pathological Animals.

Producers of milk and dairy products have been faced with the challenge of responding to European society's demand for guaranteed animal welfare production. In recent years, measures have been taken to improve animal welfare conditions on farms and evaluation systems have been developed to certify them, such as the Welfare Quality® protocol. Among the markers used for this purpose, acute phase proteins stand out, with haptoglobin being one of the most relevant. However, the diagnostic power of these tools is limited and more sensitive and specific technologies are required to monitor animal health status. Different factors such as diet, stress, and diseases modify the metabolism of the animals, altering the composition of the milk in terms of oligosaccharides, proteins, and lipids. Thus, in order to study oxidative-stress-associated lipids, a collection of well-characterized milk samples, both by veterinary diagnosis and by content of the acute stress biomarker haptoglobin, was analyzed by mass spectrometry and artificial intelligence. Two lipid species (sphingomyelin and phosphatidylcholine) were identified as potential biomarkers of health status in dairy cows. Both lipids allow for the discrimination of milk from sick animals and also milk from those with stress. Moreover, lipidomics revealed specific lipid profiles depending on the origin of the samples and the degree of freedom of the animals on the farm. These data provide evidence for specific lipid changes in stressed animals and open up the possibility that haptoglobin could also affect lipid metabolism in cow's milk.

Effects of chronic stress on bladder morphology of rats and impact of comfort food diet as an ameliorating agent

Objectives To investigate the effects of chronic stress on bladder morphology and the impact of food preference (standard or comfort foods) on the bladder of stressed rats. Methods In total, 32 Wistar male rats (3 months old) were divided into four groups: control (C), stressed (S), control + comfort food (C + CF), and stressed + comfort food (S + CF). Groups C and C + CF were maintained under normal conditions, while groups S and S + CF were subjected to chronic stress by the restraint method. Groups C and S received standard rat chow, while groups C + CF and S + CF received comfort food (Froot Loops®) and standard chow. The stress stimuli were induced daily for 2 h over 8 weeks. After 8 weeks, all animals were killed, and the bladders were removed and used for histomorphometric analysis. Results Body mass was similar among the groups. Stress did not promote differences regarding food intake, but animals receiving comfort food showed higher calories intake (in kcal/Kg) than animals receiving only standard chow. The C + CF and S + CF groups preferred comfort food over the standard chow; this preference was higher in the S + CF than in the C + CF group. The surface density of smooth muscle was reduced in stressed animals, while connective tissue and elastic system fiber content were increased in stressed groups. Further, epithelial height was increased in rats submitted to chronic stress. The surface density of elastic system fibers was decreased by the consumption of comfort food. Conclusions Chronic stress induces morphological modifications on the bladder wall and epithelium. These modifications may be related to lower urinary tract symptoms. Additionally, chronic stress caused a higher preference for comfort food intake which did not ameliorate or aggravate the stress-induced bladder alterations.

Motor Stereotypic Behaviors in Zoo Rhesus Monkeys: a Case Study of the Central Zoo, Kathmandu, Nepal

Motor stereotypic behaviors (MSBs) are a kind of repetitive behaviors performed by stressed animals and are more common in captivity. This study aimed to assess whether the MSB in captive rhesus monkeys varies between males and females, and with the extent of visitor-monkey interactions. A group of six rhesus monkeys (two adult males and four adult females; among females, two were rescued from the wild and two were captive-born) housed in the Central Zoo, Kathmandu Nepal were sampled in the study. Behavioral observations were done by focal animal sampling for 30 minutes in each session from 8:00 AM till 10:00 AM in the absence of visitors and 10:00 AM–12:00 PM in the presence of visitors. At every 10 minutes interval, the number of visitors around the cage and the level of visitor-monkey interactions were scanned. Pacing and bounce were the MSBs performed by the zoo rhesus monkeys. Females, especially the rescued ones, performed significantly more MSBs than the males. An increase in visitor-monkey interaction involved the monkeys into more begging and feeding, which in turn lowered the MSBs. The findings of this study indicate that interactive enrichment such as feeding and visitor-monkey interactions help to reduce MSBs in zoo monkeys.

Effects of chronic restraint stress in the prostate of prepubertal and adult rats.

To investigate the effects of chronic stress in the prostate of prepubertal and adult rats. Thirty-two male rats were assigned into four groups depending on the type of treatment (control or stressed) and the age at which stress was initiated (prepubertal or adult). Restraint stress stimuli were applied for six weeks. Stressed prepubertal and adult rats evaluated immediately after the last stress stimuli were named SP and SA groups, respectively. Age-matched rats were used as control groups (CP and CA). At the end of the experiment, the rats were euthanized, and prostate morphological parameters were evaluated and statistically compared. Application of stress stimuli to the SP group resulted in reduced body weight, but no prostate morphological modification was noted. The SA group showed reduced testosterone level and prostatic epithelium surface density, in comparison to CA group. Further, the prostatic lumen surface density was increased in adult stressed animals, in comparison to adult controls. The stress stimuli promoted changes in hormonal and morphological parameters in the prostate of adult stressed rats. Prepubertal stressed animals did not presented modifications of prostate morphology.

Salivary corticosterone measurement in large-billed crows by enzyme-linked immunosorbent assay.

Salivary corticosteroid measurement, as a surrogate for plasma corticosteroid levels to evaluate an animal's stress or metabolic state, commonly used in mammals. However, the validity of salivary corticosterone (CORT) measurements in birds has not yet been reported. We aimed to measure salivary CORT in crows using a commercially available CORT enzyme-linked immunosorbent assay kit. An adrenocorticotropic hormone (ACTH) challenge experiment using synthetic cosyntropin, an ACTH analogue, was conducted to compare CORT level elevations between the serum and the saliva in a 10-60 min range. Both salivary and blood CORT was significantly elevated 10 min after injecting synthetic cosyntropin. The results supported the validation of salivary CORT as a surrogate for a blood CORT in crows.

Gastroprotective and antidepressant-like effect of plum pectin (Prunus domestica L.) under water-immobilization stress in laboratory mice

Stress effects activate the processes of free radical oxidation in the organism, lead to hyper production of reactive radicals and oxidative stress, provoking the development of an inflammatory process in various parts of the gastrointestinal tract. Pectin polysaccharides together with the enzyme components of the endogenous antioxidant system contribute to the elimination of the imbalance between prooxidants and antioxidants in the tissues of stressed animals and have a gastroprotective and antidepressant-like effect. The aim of the research was to evaluate the gastroprotective, antioxidant and antidepressant-like effect of plum pectin orally administered to white laboratory mice before stressful exposure. Material and methods. In the experiment on white BALB/c mice weighing 20-25 g (90 males, 10 in each group), pectin isolated from fresh plum fruits in an artificial gastric environment was used. It was administered orally to mice 24 h before the onset of stress exposure or behavioral activity asessment. 50 animals were subjected to 5 h of water immersion stress. After this corticosterone concentration in blood plasma, and the activity of superoxide dismutase, catalase and glutathione peroxidase in the tissue supernatants of the gastrointestinal tract were determined, and the condition of the gastric mucosa was also assessed. Behavioral activity of experimental mice (n=30) was assessed in the open field and forced swimming tests. Results. The stress effect was accompanied by an increase in plasma corticosterone concentration (more than 3 fold), in the activity of superoxide dismutase, glutathione peroxidase in the tissues of the stomach wall and small intestine (17.9-28.6%) and destructive damage in the gastric mucosa compared with the indices of intact animals. Preliminary oral administration of plum pectin to animals at a dose of 80 mg per 1 kg of body weight helped to reduce the level of corticosterone and the number of stress-induced hemorrhages on the gastric mucosa, normalized the activity of antioxidant enzymes and also decreased the immobility time of mice in the forced swimming test. Preliminary oral administration of plum pectin to animals at a dose of 80 mg per 1 kg of body weight prevented an increase in the activity of antioxidant enzymes, corticosterone in the blood and the development of stress-induced hemorrhages on the gastric mucosa, and reduced the time of immobility of mice in the forced swimming test. Conclusion. Plum fruit pectin pre-administered into mice before stress prevents stress-induced damage in the tissues of the gastrointestinal tract, contributing to an increase in the body's resistance to the stress factor. Plum pectin has an antioxidant, gastroprotective and antidepressant-like effect and can be used as an ingredient in functional foods that reduce the risk of inflammatory diseases of the gastrointestinal tract under stress.

Оценка иммунотропной активности нейропептидного соединения Lys-Lys-Arg-Arg-Pro-Gly-Pro в условиях «социального» стресса

Objective: to investigate immunotropic activity of the argenine-containing neuropeptide compound Lys-Lys-Arg-Arg-Pro-Gly-Pro in conditions of "social" stress. Material and methods. The study was conducted on mongrel male rats of 6 months of age using a model of "social" stress based on the provision of permanent residence of animals in conditions of sensory contact, as a result of which submissive and aggressive types of behavior were formed. All animals were divided into groups: control I - rats who were in a cage one at a time and received water for injection in an equivalent volume; control II - groups of stressed animals with aggressive and submissive types of behavior; three groups of stressed rats were intraperitoneally injected with Lys-Lys-Arg-Arg-Pro-Gly-Pro at a dose of 100 mcg/kg/day and the comparison drug Imunofan (Arginyl-alpha-aspartyl-lysyl-valyl-thyrosyl-argininum) at an average therapeutic dose of 0.7 mcg/kg/day. The following indicators were evaluated: delayed hypersensitivity reaction index, antibody titer of direct hemagglutination reaction, phagocytic activity of peripheral blood neutrophils, leukocyte formula indicators. Results. The results obtained in the course of this study indicate that the arginine-containing neuropeptide compound Lys-Lys-Arg-Arg-Pro-Gly-Pro contributes to the correction of immune changes that occur against the background of exposure to chronic "social" stress, namely, an increase in the delayed hypersensitivity reaction index, the level of anti-erythrocyte antibodies, the total number of leukocytes and a decrease in phagocytic activity of peripheral blood neutrophils (phagocytic number and phagocytic index), as well as restoration of the percentage ratio of elements of the leukocyte formula. Conclusion. Thus, the study of the immunotropic activity of the argenine-containing neuropeptide compound Lys-Lys-Arg-Arg-Pro-Gly-Pro showed the presence of an immunocorrecting effect on the cellular and humoral links of immunity, which actualizes the need for a detailed study of the immune mechanisms of this compound.

Changes in the Content of Small Non-Coding RNAs in Spermatozoa as a Possible Mechanism of Transgenerational Transmission of the Effects of Paternal Stress: Experimental Research

It has been proven that the stress of the father can affect the phenotype of offspring, causing somatic, behavioral, hormonal and molecular changes. One of the hypothetical mechanisms responsible for the transmission of paternal effects to offspring may be a change in the spectrum of regulatory non-coding RNAs in spermatozoa. In this paper, we investigated the effect of paternal stress in models of post-traumatic stress disorder (PTSD) and depression on the representation of small RNAs (micro- and piwiRNAs) in the sperm of stressed animals. Male Wistar rats were subjected to stress in two paradigms (“stress–restress” and “learned helplessness”), which leads to the development of PTSD-like and depressive-like states in model animals, respectively. 48 days after the restress, sperm preparations were received and RNA was isolated. The spectrum of small RNAs was studied by NGS sequencing. In males with a PTSD-like condition, a change in the expression of 27 piwi RNAs and 77 microRNAs was detected compared with the control group. Among the targets of these miRNAs, it is possible to identify genes whose products may be involved in such mechanisms of transmission of paternal effects to offspring as changes in DNA methylation, histone modifications and RNA interference (Dnmt3a, Setd5, Hdac1, Mllt10, Mtdh), as well as genes associated with the functioning of insulin-like growth factor 2, the expression of which as previously shown, it is altered in the central nervous system in the offspring of males with a PTSD-like condition (Igf2, Igf2bp2, Igf2r). No changes in the representation of small RNAs were registered in males with a simulated depression-like state. The results indicate a pronounced effect of paternal stress on the spectrum of short non-coding RNAs in sperm cells in rats, however, it depends on the nature of the stress effect.