Stressed Female Rats Research Articles

Oxidative stress-induced by different stressors alters kidney tissue antioxidant markers and levels of creatinine and urea: the fate of renal membrane integrity

The cellular integrity of the kidney in homeostatic regulation has constantly been compromised by oxidative stress following exposure to varying nature of stressor present within the environment. The objective of the work was to evaluate the renal effect of the different stressor stimuli applied. Twenty-four adult female rats weighing averagely 160–200 g and within the ages of 12–14 weeks were used for experiment-1, while 12 offspring were utilized for experiment-2. Three stress models namely; restraint, mirror chamber and cat intruder stressors were used. Tissues were isolated from the animal and homogenized for tissue antioxidant assay. Serum was collected for assays of urea and creatinine for the kidney function test using ELISA. Data collected were analyzed for Mean ± SEM using One Way ANOVA. The present study revealed that exposure of rats to different stressors reduced relative kidney weights but did not significantly alter serum creatinine concentration in the Wistar rats, although the concentrations were slightly increased compared to controls. Urea concentration was significantly (p < 0.05) increased in rats exposed to restraint and intruder stressors. Exposure to a mirror chamber stressor did not significantly alter urea concentration. Offspring from parents of stressed female rats exhibited a significant (p < 0.05) increase in serum urea level, minimal increase in serum creatinine levels. GSH and GST levels showed no significant difference when compared to control group, whereas, GPx were significantly (p < 0.05) decreased irrespective of the stressor applied. SOD activity were significantly (p < 0.05) reduced in the group exposed to restraint or cat intruder stressor. CAT activities were significantly (p < 0.05) reduced in the rats exposed to restraint or cat intruder stressor. In all, the different stress model altered the antioxidant capacity of the kidney tissues. Exposure of rats to a stressful condition of the different nature of stressor has the tendency of compromising the functional integrity of the kidney, thus, with the potency of complicating female renal function.

Spinal alarmin HMGB1 and the activation of TLR4 lead to chronic stress-induced nociceptive hypersensitivity in rodents

Chronic stress affects millions of people around the world, and it can trigger different behavioral disorders like nociceptive hypersensitivity and anxiety, among others. However, the mechanisms underlaying these chronic stress-induced behavioral disorders have not been yet elucidated. This study was designed to understand the role of high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) in chronic stress-induced nociceptive hypersensitivity. Chronic restraint stress induced bilateral tactile allodynia, anxiety-like behaviors, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) and activation of spinal microglia. Moreover, chronic stress enhanced HMGB1 and TLR4 protein expression at the dorsal root ganglion, but not at the spinal cord. Intrathecal injection of HMGB1 or TLR4 antagonists reduced tactile allodynia and anxiety-like behaviors induced by chronic stress. Additionally, deletion of TLR4 diminished the establishment of chronic stress-induced tactile allodynia in male and female mice. Lastly, the antiallodynic effect of HMGB1 and TLR4 antagonists were similar in stressed male and female rats and mice. Our results suggest that chronic restraint stress induces nociceptive hypersensitivity, anxiety-like behaviors, and up-regulation of spinal HMGB1 and TLR4 expression. Blockade of HMGB1 and TLR4 reverses chronic restraint stress-induced nociceptive hypersensitivity and anxiety-like behaviors and restores altered HMGB1 and TLR4 expression. The antiallodynic effects of HMGB1 and TLR4 blockers in this model are sex independent. TLR4 could be a potential pharmacological target for the treatment of the nociceptive hypersensitivity associated with widespread chronic pain.

URB597 attenuates stress-induced ventricular structural remodeling by modulating cytokines, NF-kB and JAK2/STAT3 pathways in female and male rats.

Endocannabinoids act as a stress response system simultaneously the modulation of this system has emerged a novel approach for the therapy of cardiovascular disorders. We investigated the protective effects of the chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on morphology, pro-inflammatory and anti-inflammatory cytokine, the cytoplasm-nuclear distribution of JAK2/STAT3, NF-kB, and Nrf2/HO-1 signaling in the left ventricle of female and male rats exposed to chronic unpredictable stress. Our results show that URB597 treatment exhibits an antidepressant-like effect, decreases the heart/body weight ratio, prevents the hypertrophy of cardiomyocytes, and reduces the increased level of IL-6 in the wall of the left ventricle of stressed female and male rats. The phosphorylation levels of JAK2 and STAT3 in the ventricle of male rats treated with URB597 declined, whereas in female rats the decrease of STAT3 was observed. In addition, URB597 reduced increased NF-κB in both females and males and increased the expression of Nrf2 and HO-1 protein in the cytosol of male rats whereas did not affect their levels in females. The cardioprotective effects of URB597 could be linked to the ability to inhibit the JAK2 in males and the STAT3 inflammatory signaling pathways in both females and males.

Chronic stress decreases fertility parameters in female rats

Multiple effects of stress on health have been reported; however, reproductive alterations in oocytes and cumulus cells have not been fully described. In females, chronic stress has been shown to produce alterations in the estrous cycle, to decrease oocyte in vivo maturation, and to increase the percentage of abnormal oocytes. The aim of this study was to evaluate whether the oocytes from chronically stressed female rats could recover and mature in vitro by providing them with all the necessary culture conditions, as well as to evaluate the functionality of the GAP junctions, and the viability and DNA integrity of the cumulus cells, which are crucial for the complete maturation and development of the oocyte. For this, rats were stressed daily by cold water immersion (15 °C) during 15 min for 30 consecutive days. Corticosterone serum levels in rats increased as an indicator of stress. Chronic stress decreased the percentage of in vitro matured oocytes because the cumulus cells presented irreparable damage to their DNA that led to their death, being unable to establish bidirectional communication with the oocyte for its meiotic resumption through the GAP junctions, which were also damaged. These findings could partially explain an association between stress and infertility.

Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats

Introduction: The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS). Material and Methods: Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol. Catecholamines’ plasma levels and catecholamines’ levels in adrenal medulla were examined using Elabscience ELISA kits. Western blot analysis was used to detect the protein in the medulla. Results: The results of our experiment showed that adrenal weights and catecholamine of unstressed control were higher in females and that CUS induced further enlargement of adrenal glands and catecholamine content and its synthesis compared to male rats. CUS caused an increase of plasma norepinephrine and depletion of norepinephrine content as well as unchanged synthesis and degradation of catecholamine in the adrenal medulla of male rats. URB597 reduced enlarged adrenals and catecholamine content and its synthesis in stressed female rats. URB597 reduces increased plasma norepinephrine and restores its content in the adrenal medulla, unchanging the expression of enzyme synthesis, while reduced protein levels of monoamine oxidase A in male rats are exposed to CUS. Discussion: Our results support the role of endocannabinoids as an antistress mechanism that inhibits elevated adrenomedullary activation and promotes its recovery to baseline in both male and female stressed rats.

Chronic Stress Detrimentally Affects In Vivo Maturation in Rat Oocytes and Oocyte Viability at All Phases of the Estrous Cycle.

Stress has been considered as one of the causes of decreased reproductive function in women. However, direct evidence of the effect of chronic stress on oocytes depending on estrous cycle phases is limited. The present study aimed to evaluate the impact of chronic stress on the viability, integrity, and maturation of rat oocytes depending on estrous cycle phases, specifically proestrus, estrus, and diestrus. For this purpose, adult female rats were stressed daily by cold water immersion (15 °C) for 30 consecutive days. In chronically stressed female rats, irregular estrous cyclicity, increased corticosterone levels, decreased oocyte viability, and an increased percentage of abnormal oocytes were obtained in all the estrous cycle phases, resulting in reduced oocyte maturation during proestrus. Oocyte maturation disturbed by chronic stress is a crucial factor by which chronic stress disrupts female reproduction.

Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress

RationaleThe combination of several risk factors (sex, a prior underlying psychiatric condition, or early drug initiation) could induce the emergence of negative affect during cocaine abstinence and increase the risk of developing addiction. However, most prior preclinical studies have been centered in male rodents, traditionally excluding females from these analyses.ObjectivesTo ascertain the behavioral and neurochemical consequences of adolescent cocaine exposure when the combination of several risk factors is present (female, early-life stress).MethodsWhole litters of Sprague–Dawley rats were exposed to maternal deprivation for 24 h on postnatal day (PND) 9. Cocaine was administered in adolescence (15 mg/kg/day, i.p., PND 33–39). Negative affect was assessed by several behavioral tests (forced swim, open field, novelty-suppressed feeding, sucrose preference). Hippocampal cell fate markers were evaluated by western blot (FADD, Bax, cytochrome c) or immunohistochemistry (Ki-67; cell proliferation).ResultsMaternal deprivation is a suitable model of psychiatric vulnerability in which to study the impact of adolescent cocaine in female rats. While adolescent cocaine did not alter affective-like behavior during adolescence, a pro-depressive–like state emerged during adulthood, exclusively in rats re-exposed to cocaine during abstinence. FADD regulation by cocaine in early-life stressed female rats might contribute to certain hippocampal neuroadaptations with some significance to the observed induced negative affect.ConclusionsAdolescent cocaine induced persistent negative affect in female rats exposed to early-life stress, highlighting the risk of early drug initiation during adolescence for the emergence of negative reinforcement during abstinence likely driving cocaine addiction vulnerability, also in female rats.

Модуляция воспалительного болевого и гормонального ответов стрессом в препубертатный период развития у пренатально стрессированных взрослых самцов и самок крыс

Stress during critical periods of development can have an abnormal effect on the development of the hypothalamic-pituitary-adrenocortical system (HPA axis), morphogenetic and neurochemical processes of the brain, increasing the risk of psychopathologies. Along with this, there is an increasing number of works indicating the possible adaptive influence of stress. This issue is of practical value which explains the popularity of studies in the mechanisms by which stress at an early age increases the body’s resistance to stress. The available data suggest an important contribution of the serotonergic system to individual differences in the susceptibility to stress events further in life. The balance between the HPA axis and serotonergic system during development is one of the main conditions for the normal functioning of the stress system. We were the first to use pain stress to study the mechanisms of stress neutralization by another pain stress. Previously, we showed an increase in inflammatory pain response in prenatally stressed adult male and female rats. The aim of this work was to investigate the effect of stress during the prepubertal period of development on inflammatory pain, anxiety / depression disorders, and stress reactivity of the HPA axis in prenatally stressed adult male and female rats. In addition, we studied the question of whether prepubertal stress may change the effect of the 5-HT1A receptor agonist buspirone and the serotonin reuptake inhibitor fluoxetine administered to depressed rats during pregnancy on behavioral and hormonal responses in the adult prenatally stressed offspring.

The involvement of Notch1 signaling pathway in mid-aged female rats under chronic restraint stress

Women are vulnerable to adverse stress events, especially during perimenopause. Substantial evidence has associated the impaired neuronal plasticity with abnormal behaviors under stressful conditions in animals. The Notch signaling pathway is critical for neuronal plasticity in the structure and function of brain areas. In this study, the mid-aged female rats were subjected to chronic restraint stress(CRS) in combination with isolated rearing for 6 weeks. The behavior tests and HPA activity were conducted to evaluate the model. The mRNA and protein levels of Notch1 signaling related genes in the hippocampus(HIP) and prefrontal cortex(PFC) were analyzed by RT-qPCR and western blotting. The promoter methylation levels were measured by bisulfite sequencing PCR analysis. CRS induced depression-like and anxiety-like behaviors in mid-aged stressed females, as shown by decreased locomotor activity, sucrose consumption and increased HPA activity. Moreover, after CRS, the rats exhibited decreased mRNA and protein levels in Jagged1, Notch1 and Hes5 in the HIP and Notch1, Hes1 and Hes5 in the PFC. However, there were no significant promotor methylation changes between the stressed and control female rats. These findings suggest that Notch1 signaling pathway may contribute to the behavioral changes following CRS in mid-aged female rats and the upstream cause of the gene expression changes needs to be further investigated.

Neuroendocrine disruption is associated to infertility in chronically stressed female rats

Infertility is a growing worldwide public health problem, and stress is a main factor exerting detrimental effects on female reproduction. However, knowledge regarding the neuroendocrine changes caused by chronic stress in females is limited. Therefore, this study assessed the effects of stress on hormones that control female reproduction during the proestrus and diestrus stages of the estrous cycle, as well as its effects on fertility. Adult females were assigned to either a control or a stress group. Stress consisted of exposure, for 15 min, to cold-water immersion daily for 30 days. Estrous cyclicity, female sexual behavior, as well as hypothalamic kisspeptin, gonadotropin releasing hormone (GnRH) content, serum luteinizing hormone (LH), estradiol (E2), progesterone (P4), corticosterone (CORT) and fertility were assessed after chronic stress. The results show that chronically stressed females exhibited disrupted estrous cyclicity, decreased receptivity, low pregnancy rates and lower numbers of fetuses. The content of Kisspeptin and GnRH in the Anteroventral Periventricular/medial Preoptic Area decreased during proestrus, while Kisspeptin increased in the Arcuate nucleus in proestrus and diestrus. Serum LH decreased only during proestrus, whereas E2 and P4 concentrations decreased during proestrus and diestrus, with a concomitant increase in CORT levels in both stages. As a whole, these results indicate that chronic stress decreases Kisspeptin content in AVPV nucleus and GnRH in POA in females, and might induce disruption of the LH surge, consequently disrupting estrous cyclicity and fertility, leading to lower rates of pregnancy and number of fetuses.

The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats

The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats. The results show that CUS increases anxiety-like behaviors and that URB597 had an anxiolytic effect on chronically stressed animals of both sexes. CUS induced the expression of plasma interleukin – 6 (IL-6), interleukin – 10 (IL-10) and IL-6 in the spleen, whereas the expression of IL-10 was reduced in the spleen of both sexes. URB597 treatment did not cause changes in IL-6 in plasma or the spleen, whereas it increased IL-10 in the spleen in CUS animals of both sexes. CUS caused a significant depletion of noradrenaline content in the spleen of female rats and a reduction in noradrenaline uptake in the spleen of female rats, while stressed males had a small but insignificant decrease of splenic noradrenaline levels and an enhanced uptake. The FAAH inhibitor URB597 enhances reduced noradrenaline content, affecting its uptake directly at the level of the spleen. It gives rise to the possibility that endocannabinoids exert a neurorestorative effect on the sympathetic nerve system and cell-mediated immune responses in the spleen of chronically stressed rats.

Familiarity modulates social approach toward stressed conspecifics in female rats.

Familiarity between conspecifics may influence how social affective cues shape social behaviors. In a social affective preference test, experimental rats, when given the choice to explore an unfamiliar stressed or a naive adult, will avoid interaction with a stressed conspecific. To determine if familiarity would influence social interactions with stressed conspecifics, male and female test rats underwent 2 social affective preference tests in isosexual triads where an experimental rat was presented with a naïve and a stressed target conspecific who were either familiar (cagemate) or unfamiliar. Male and female experimental rats avoided stressed unfamiliar conspecifics. However, experimental female rats demonstrated a preference to interact with their stressed, familiar cagemates. Male and female rats exhibited more self-grooming and immobility behavior in the presence of stressed conspecifics, which may indicate emotion contagion. These findings suggest a sex-specific role of familiarity in social approach and avoidance, and warrant further mechanistic exploration.

Neuroinflammatory priming to stress is differentially regulated in male and female rats

Exposure to stressors can enhance neuroinflammatory responses, and both stress and neuroinflammation are predisposing factors in the development of psychiatric disorders. Females suffer disproportionately more from several psychiatric disorders, yet stress-induced changes in neuroinflammation have primarily been studied in males. Here we tested whether exposure to inescapable tail shock sensitizes or ‘primes’ neuroinflammatory responses in male and female rats. At 24 h post-stress, male and female rats exposed to a peripheral immune challenge enhanced neuroinflammatory responses and exacerbated anxiety- and depressive-like behaviors. These changes are likely glucocorticoid dependent, as administering exogenous CORT, caused a similar primed inflammatory response in the hippocampus of male and female rats. Further, stress disinhibited anti-inflammatory signaling mechanisms (such as CD200R) in the hippocampus of male and female rats. In males, microglia are considered the likely cellular source mediating neuroinflammatory priming; stress increased cytokine expression in ex vivo male microglia. Conversely, microglia isolated from stressed or CORT treated females did not exhibit elevated cytokine responses. Microglia isolated from both stressed male and female rats reduced phagocytic activity; however, suggesting that microglia from both sexes experience stress-induced functional impairments. Finally, an immune challenge following either stress or CORT in females, but not males, increased peripheral inflammation (serum IL-1β). These novel data suggest that although males and females both enhance stress-induced neuroinflammatory and behavioral responses to an immune challenge, this priming may occur through distinct, sex-specific mechanisms.

Convergence of glycogen synthase kinase 3β and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats

Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3β, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3β-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3β targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress.Stress induced sex-specific GSK3β-targeted phosphorylation of pGR171 in the nucleus of the hippocampus of stressed animals. Namely, while in females stress triggered coupled action of GSK3β-pGR171 signaling, in males changes in pGR171 levels did not correspond to GSK3β activity. On the other hand, fluoxetine managed to up-regulate this pathway in sex-unbiased manner. Furthermore, fluoxetine reverted stress-induced changes in most of the analyzed genes in males, CRH, 5-HT1a and p11, while in females its effect was limited to CRH. These data further suggest that pGR171 signaling affects cellular localization of GR in response to chronic stress and fluoxetine in both sexes.Collectively, our results describe a novel convergence point between GR signaling and GSK3β pathway in rat hippocampus in response to stress and fluoxetine in both sexes and its involvement in fluoxetine-regulated brain function in males.

Age- and Sex-Dependent Impact of Repeated Social Stress on Intrinsic and Synaptic Excitability of the Rat Prefrontal Cortex.

Stress is implicated in psychiatric illnesses that are characterized by impairments in cognitive functions that are mediated by the medial prefrontal cortex (mPFC). Because sex and age determine stress vulnerability, the effects of repeated social stress occurring during early adolescence, mid-adolescence, or adulthood on the cellular properties of male and female rat mPFC Layer V neurons in vitro were examined. Repeated resident–intruder stress produced age- and sex-specific effects on mPFC intrinsic and synaptic excitability. Mid-adolescents were particularly vulnerable to effects on intrinsic excitability. The maximum number of action potentials (APs) evoked by increasing current intensity was robustly decreased in stressed male and female mid-adolescent rats compared with age-matched controls. These effects were associated with stress-induced changes in AP half-width, amplitude, threshold, and input resistance. Social stress at all ages generally decreased synaptic excitability by decreasing the amplitude of spontaneous excitatory postsynaptic potentials. The results suggest that whereas social stress throughout life can diminish the influence of afferents driving the mPFC, social stress during mid-adolescence additionally affects intrinsic characteristics of mPFC neurons that determine excitability. The depressant effects of social stress on intrinsic and synaptic mPFC neurons may underlie its ability to affect executive functions and emotional responses, particularly during adolescence.

Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats

Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner.

Features of the Action of Combined Administration of NAN-190 and Ketanserin with Low-Dose 17β-Estradiol on Depression-Like Behavior in Prenatally Stressed Rats

The aim of the present work was to compare the effects of blockade of 5-HT1A or 5-HT2A/2C serotonin receptors on depression-like behavior in adult female rats with experimental estrogen deficiency whose mothers had been subjected to prenatal stress during pregnancy. Two weeks after removal of the ovaries, ovariectomized (OE) prenatally stressed female rats received chronic administration of the 5-HT1A serotonin receptor antagonist NAN-190 (0.1 mg/kg, i.p.) or the 5-HT2A/2C serotonin receptor antagonist ketanserin (0.1 mg/kg, i.p.) alone or in combination with a low dose of 17β-estradiol (0.5 μg/rat, s.c.) for 14 days before behavior tests started and then until tests were completed. The behavioral methods used were the Porsolt test and the open field test. The results showed that chronic administration of NAN-190 to OE prenatally stressed females led to a prodepressive effect, while the combination of NAN-190 with low-dose 17β-estradiol, conversely, had an antidepressant effect in the Porsolt test. In the open field test, these two experimental groups of rats showed decreases in the amounts of grooming reactions, vertical motor activity, and exploratory activity. Administration of ketanserin to OE prenatally stressed females produced an antidepressant effect, as compared with control animals. However, combined administration of ketanserin and low-dose 17β-estradiol to OE prenatally stressed females had no positive effect on the behavior of the animals in the Porsolt test.

LPS reduces BDNF and VEGF expression in the structures of the HPA axis of chronic social stressed female rats

Imbalance of brain neural circuitry induced by chronic stress leads to dysregulation of the HPA axis and dysfunction of neuroplasticity. The aim of the study was to investigate the influence of acute immunostimulation on the expression and protein level of BDNF and VEGF in the hypothalamus, pituitary and plasma of female rats subjected to chronic social instability stress. Rats were subjected to 4-week stress procedure, including phases of isolation and crowding, alternated in an unpredictable manner. On the last experimental day, the rats in the estrus phase were injected ip. with LPS (1mg/kg). All experiments were performed on females being in the same phase of the estrus cycle to avoid alterations in neurotrophin expression. An increase in relative adrenal and thymus weights in the stressed rats were observed. Chronic stress affected more strongly VEGF but not BDNF in the hypothalamus and pituitary gland. In the stressed rats, LPS decreased BDNF and VEGF mRNA levels in both structures and plasma BDNF concentrations. Optical density of VEGF immunoreactivity in the supraoptic nucleus was increased after LPS administration in the stressed rats as compared to the saline-treated stressed group. It may be assumed that chronic social stress makes the SOR neurons sensitive to a peripheral proinflammatory stimulus. Our results indicate that chronic stress enhances vulnerability of BDNF and VEGF response to neuroinflammation in the examined structures, which may be one of the reasons for its role in triggering affective diseases.

The Effects of Immobilization Stress on Serum Ghrelin Level, Food Intake and Body Weight in Male and Female Rats

Background: Stress causes various physiological, histological and behavioral changes. Objectives: The goal of the present study was to evaluate the effects of chronic immobilization stress on plasma ghrelin level, food intake and body weight in both male and female rats. Materials and Methods: Twenty male and 20 female rats were studied. These animals were divided to four groups (two control groups and two experimental groups). In the experimental groups, rats were exposed to immobilization stress for 14 days. On the fourteenth day serum ghrelin level was measured by the ELISA kit. Food consumption and body weight change during 14 days were also recorded. Student t-test was used to compare mean among the groups. Results: In male rats, immobilization stress significantly (P ˂ 0.0001) increased serum ghrelin level and decreased body weight as compared with the control group (P ˂ 0.0001). Food consumption significantly (P ˂ 0.0001) increased in stressed female and male rats. Conclusions: The results of this study indicate that the effect of stress on serum ghrelin level and body weight is gender-depended.

Adrenal response of male rats exposed to prenatal stress and early postnatal stimulation

Stress in pregnant rats caused by chronic immobilization alters the pattern of secretion of corticosterone and modifies the hypothalamic-pituitary-adrenal axis (HPA) of the fetus. Early postnatal handling, however, may reverse the effects of increased secretion of corticosterone. We investigated the effects of prenatal stress and postnatal handling on the activity of the HPA axis of male offspring of stressed female rats. Male 90-day-old rats from four groups were investigated: prenatally stressed animals without postnatal handling, prenatally stressed animals with postnatal handling, unstressed control animals with postnatal handling, and unstressed control animals without postnatal handling. After sacrifice, the adrenal glands were weighed to determine the adrenal-somatic index. Apoptosis was evaluated by TUNEL assay and active caspase-3 expression. We found that the adrenal gland cortex:medulla ratio increased in animals with prenatal stress and that eventually the stress caused apoptosis. Handling newborns to simulate maternal activity ameliorated some of the negative effects of prenatal stress.