Stress In Adult Rats Research Articles

Sex-specific behavioral, cardiac, and neuroendocrine responses to repeated witness social stress in adult rats

In humans, sex disparities exist in the prevalence of social stress-related disorders, yet our understanding of the predisposing factors and underlying mechanisms is still elusive. Also at the preclinical level, the investigation of sex differences in social stress responses is limited. In this study, adult male and female wild-type Groningen rats were repeatedly exposed to witness social defeat stress (WS) to assess sex-specific behavioral, neuroendocrine, and cardiac responses to the same social stress paradigm. Male and female rats bore witness to an aggressive social defeat episode between two males for nine consecutive days or were exposed to a control (CTR) procedure. Stress-related parameters were assessed in correspondence to the first and last WS/CTR exposure and also during subsequent exposure to the stress context alone in the absence of social defeat. During WS, rats of both sexes displayed larger amounts of burying behavior and smaller amounts of rearing and grooming behaviors, but with a greater extent in female witnesses. Cardiac autonomic responses to WS were similar between the sexes, yet only females displayed higher plasma corticosterone levels after the first WS exposure compared to CTRs, and had a larger corticosterone increase than male witnesses upon repeated WS. Exposure to the stress context alone (i.e., without the presence of the aggressive resident rat) elicited greater amount of burying behavior and more pronounced and persistent tachycardic responses in females than males with a history of WS. Our findings suggest sex-disparities in the response of adult rats to WS at multiple behavioral, cardiac, and neuroendocrine levels, highlighting the utility of this social stress paradigm for investigating predisposing factors and pathophysiological mechanisms underlying sex-specific vulnerabilities to stress-related pathologies.

Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3h a day for 10days. When adults, these animals were divided into groups and submitted to treatment for 14days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Effects of Maternal Separation and Subsequent Stress on Behaviors and Brain Monoamines in Rats.

Childhood adversity can induce maladaptive behaviors and increase risk for affective disorders, post-traumatic stress disorder, personality disorders, and vulnerability to stress in adulthood. Deprivation of maternal care interrupts brain development through the disturbance of various neurotransmitters, however, the details remain unclear. The features of the symptoms of disorders are largely determined by early stress protocol, genetic characteristics (line), and the sex of the animals. The purpose of current study was (1) to assess behavioral changes in adult Wistar rats of both sexes after early life stress; (2) to determine the levels of monoamines in brain structures involved in the motor, emotional, and social reactions in rats aged 1 and 2 months; and (3) to determine the level of monoamines after physical or emotional stress in adult rats. The rat pups were separated from their dams and isolated from siblings in tight boxes at a temperature of 22-23 °C for 6 h during postnatal days 2-18. The data were processed predominantly using two-way analysis of variance and the Newman-Keys test as the post hoc analysis. The adult rats demonstrated an increase in motor activity and aggressiveness and a decrease in levels of anxiety and sociability. Behavioral disturbances were accompanied by region-, sex-, and age-dependent changes in the levels of monoamines and their metabolites. The dopaminergic and noradrenergic systems were found to be sensitive to psycho-emotional stress.

Vulnerability and resilience to cardiovascular and neuroendocrine effects of stress in adult rats with historical of chronic stress during adolescence

AimsThis study investigated the influence of exposure to stress during adolescence in autonomic, cardiovascular, neuroendocrine and somatic changes evoked by chronic stress in adult rats. Main methodsAnimals were subjected to a 10-days protocol of repeated restraint stress (RRS, habituating) or chronic variable stress (CVS, non-habituating) during adolescence, adulthood, or repeated exposure to either RRS or CVS in adolescence and adulthood (adolescence+adulthood group). The trials to measure autonomic, cardiovascular, neuroendocrine and somatic changes in all experimental groups were performed in adulthood. Key findingsCVS increased basal circulating corticosterone levels and caused adrenal hypertrophy in the adolescence+adulthood group, an effect not identified in animals subjected to this stressor only in adulthood or adolescence. CVS also caused a sympathetically-mediated resting tachycardia in the adulthood group. This effect of CVS was not identified in the adolescence+adulthood group once the increased cardiac sympathetic activity was buffered by a decrease in intrinsic heart rate in these animals. Moreover, the impairment in baroreflex function observed in the adulthood group subjected to CVS was shifted to an improvement in animals subjected to repeated exposure to this stressor during adolescence and adulthood. The RRS in the adolescence+adulthood group caused a sympathetically-mediated resting tachycardia, which was not observed in the adulthood group. SignificanceOur findings suggest that enduring effects of adverse events during adolescence included a vulnerability to neuroendocrine changes and a resilience to autonomic and cardiovascular dysfunctions caused by the CVS. Furthermore, results of RRS indicated a vulnerability to cardiovascular and autonomic changes evoked by homotypic stressors.

Differential impact of two paradigms of early-life adversity on behavioural responses to social defeat in young adult rats and morphology of CA3 pyramidal neurons

Early life stress (ELS) is an important factor in programing the brain for future response to stress, and resilience or vulnerability to stress-induced emotional disorders. The hippocampal formation, with essential roles in both regulating the stress circuitry and emotionality, contributes to this adaptive programing. Here, we examined the effects of early handling (EH) and maternal deprivation (MD) as mild and intense postnatal stressors, respectively, on the behavioural responses to social defeat stress in young adulthood. We also evaluated the interaction of mild and intense ELS with later social defeat (SD) stress on the morphology and dendritic spine density of Golgi-cox-stained CA3 hippocampal neurons. SD stress in adult rats, as expected, increased anxiety and depressive-like behaviours in the open field, elevated plus-maze and forced swimming test. These effects were associated with reduction of dendritic spines and soma size of CA3 neurons. Both behavioural and structural alterations were significantly ameliorated in socially defeated rats that experienced early handling (EH-SD). Basal dendrites of CA3 neurons in EH-SD rats also showed longer dendrites and more intersections with Sholl circles in the distal portion, compared to both control and SD rats. On the other hand, in socially defeated rats with maternal deprivation experience (MD-SD) the stress-induced behavioural and structural alterations were generally intensified compared to SD rats. In MD-SD rats, apical dendrites of CA3 neurons demonstrated remarkable retraction; an effect that was not detected in SD rats. The reduction of dendritic spines density on the apical dendrites of CA3 neurons was also more pronounced in MD-SD rats compared to SD rats. Dendritic arbors and spines comprise the major neuronal substrate for the circuit connectivity, and cell region-specific alterations of dendrites and spines in CA3 neurons reveal plausible mechanisms that can underlie the impact of different ELSs on risk for affective disorders in response to social stress in adulthood.

Neurocan regulates vulnerability to stress and the anti-depressant effect of ketamine in adolescent rats.

Depression is more prevalent among adolescents than adults, but the underlying mechanisms remain largely unknown. Using a subthreshold chronic stress model, here we show that developmentally regulated expressions of the perineuronal nets (PNNs), and one of the components, Neurocan in the prelimbic cortex (PrL) are important for the vulnerability to stress and depressive-like behaviors in both adolescent and adult rats. Reduction of PNNs or Neurocan with pharmacological or viral methods to mimic the expression of PNNs in the PrL during adolescence compromised resilience to stress in adult rats, while virally mediated overexpression of Neurocan reversed vulnerability to stress in adolescent rats. Ketamine, a recent-approved drug for treatment-resistant depression rescued impaired function of Parvalbumin-positive neurons function, increased expression of PNNs in the PrL, and reversed depressive-like behaviors in adolescent rats. Furthermore, we show that Neurocan mediates the anti-depressant effect of ketamine, virally mediated reduction of Neurocan in the PrL abolished the anti-depressant effect of ketamine in adolescent rats. Our findings show an important role of Neurocan in depression in adolescence, and suggest a novel mechanism for the anti-depressant effect of ketamine.

Escitalopram alters the hypothalamic OX system but does not affect its up-regulation induced by early-life stress in adult rats.

We hypothesized that there is a relationship between the orexinergic system (OX) alterations and changes elicited by escitalopram or venlafaxine in adult rats subjected to maternal separation (MS). This animal model of childhood adversity induces long-lasting consequences in adult physiology and behavior. Male Wistar rats from the control and MS groups were injected with escitalopram or venlafaxine (10 mg/kg) IP from postnatal day (PND) 69–89. Adult rats were subjected to behavioral assessment, estimation of hypothalamic-pituitary-adrenal (HPA) axis activity and analysis of the OX system (quantitative PCR and immunohistochemistry) in the hypothalamus and amygdala. MS caused anxiety- and depressive-like behavior, endocrine stress-related response, and up-regulation of the OX system in the hypothalamus. Escitalopram, but not venlafaxine, increased the activity of hypothalamic OX system in the control rats and both drugs had no effect on OXs in the MS group. The disturbed signaling of the OX pathway may be significant for harmful long-term consequences of early-life stress. Our data show that the normal brain and brain altered by MS respond differently to escitalopram. Presumably, anti-anxiety and antidepressant effects of this drug do not depend on the activity of hypothalamic OX system.

Developmental effects of early-life stress on dopamine D2 receptor and proteins involved in noncanonical D2 dopamine receptor signaling pathway in the prefrontal cortex of male rats.

Dopamine neurotransmission is implicated in multiple neuropsychiatric disorders, most strikingly in Parkinson's disease, bipolar disorder, attention-deficit hyperactivity disorder and schizophrenia. In addition to canonical pathway, D2-receptor (D2R) exerts some of its biological actions through regulating the activity of Akt and GSK3, which in turn were found to be altered in several psychiatric illnesses. The present study examined the impacts of maternal separation, an early-life stress model which has been associated with disturbed neurodevelopment and appearance of many psychiatric disorders, on developmental changes in dopamine concentration and the expression of D2Rs, Akt and GSK-3β in the medial prefrontal cortex (PFC; a key target of stress) in adolescent and young adult male rats. Maternal separation was performed 3 h per day from postnatal days 2 to 11. The PFC protein and dopamine contents were determined using western blotting analysis and Eliza, respectively. Results indicated long-term increases in the prefrontal dopamine levels in stressed adolescent and young adult male rats, accompanied by significant downregulation of D2R as well as upregulation of p-Akt and GSK-3β contents in stressed adolescence compared to controls, with all protein levels that returned to control values in stressed adult rats. Our findings suggest that early-life stress differentially modulates prefrontal D2R/Akt/GSK-3β levels during development. Since adolescence period is susceptible to the onset of specific mental illnesses, disruption of noncanonical components of D2R signaling during this critical period may have an important role in programming neurobehavioral phenotypes in adulthood and manipulations influencing Akt/GSK-3β pathway may improve the expression of specific dopamine-related behaviors and the effects of dopaminergic drugs.

Social Defeat Stress During Early Adolescence Confers Resilience Against a Single Episode of Prolonged Stress in Adult Rats.

Early-life adverse experiences (first hit) lead to coping strategies that may confer resilience or vulnerability to later experienced stressful events (second hit) and the subsequent development of stress-related psychopathologies. Here, we investigated whether exposure to two stressors at different stages in life has long-term effects on emotional and cognitive capabilities, and whether the interaction between the two stressors influences stress resilience. Male rats were subjected to social defeat stress (SDS, first hit) in adolescence and to a single episode of prolonged stress (SPS, second hit) in adulthood. Behavioral outcomes, hippocampal expression of brain-derived neurotrophic factor, and plasma corticosterone levels were tested in adulthood. Rats exposed to both stressors exhibited resilience against the development of stress-induced alterations in emotional behaviors and spatial memory, but vulnerability to cued fear memory dysfunction. Rats subjected to both stressors demonstrated resilience against the SDS-induced alterations in hippocampal brain-derived neurotrophic factor expression and plasma corticosterone levels. SPS alone altered locomotion and spatial memory retention; these effects were absent in SDS-exposed rats later exposed to SPS. Our findings reveal that exposure to social stress during early adolescence influences the ability to cope with a second challenge experienced later in life.

Social Defeat Stress during Early Adolescence Confers Resilience against a Single Episode of Prolonged Stress in Adult Rats

Social Defeat Stress during Early Adolescence Confers Resilience against a Single Episode of Prolonged Stress in Adult Rats

Melatonin Ameliorates Valproic Acid-Induced Neurogenesis Impairment: The Role of Oxidative Stress in Adult Rats.

Background Valproic acid (anticonvulsant medication) has been found to inhibit histone deacetylase activity and suppress hippocampal neurogenesis, which causes memory impairment in both humans and rodents. The neurohormone melatonin, which regulates mammalian seasonal and circadian physiology, has recently been shown to have neuroprotective properties, counteracting memory impairment associated with VPA-caused hippocampal neurogenesis reduction. This study is aimed at investigating the molecular mechanisms of melatonin associated with VPA-induced hippocampal neurogenesis and memory impairment. Methods Male Spraque-Dawley rats received VPA (300 mg/kg) twice daily or melatonin (8 mg/kg/day) or some rats were given melatonin for 14 days during VPA administration. Results The VPA-treated rats showed a significant increase in malondialdehyde (MDA) levels in the hippocampus and p21-positive cells in the subgranular zone (SGZ) of the dentate gyrus (DG) but decreased superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. Moreover, VPA significantly decreased levels of nestin, Notchl, nuclear factor erythroid 2-related factor 2 (Nrf2), doublecortin (DCX), sex determining region Y-box 2 (SOX2), and brain-derived neurotrophic factor (BDNF). Conclusions We found that melatonin was able to counteract these neurotoxic effects, acting as a neuroprotectant in VPA-induced memory hippocampal neurogenesis impairment by preventing intracellular oxidative stress and increasing antioxidant activity.

Sex-divergent long-term effects of single prolonged stress in adult rats

Single prolonged stress (SPS) is an experimental model that recapitulates in rodents some of the core symptoms of post-traumatic stress disorder (PTSD). Although women have a two-fold greater risk to develop PTSD, most preclinical studies have been carried out in males. Furthermore, the long-term effects of behavioral alterations induced by SPS have been rarely investigated. Here, we evaluated the long-term effects of SPS on PTSD-relevant behavioral domains in rats and whether these effects were sex-dependent. To this aim, separate cohorts of male and female adult rats were subjected to SPS and, 30 days later, long-term effects were assessed. We found that SPS exposure reduced locomotor activity in both sexes in an open field task. Males only showed increased anxiety-like behavior in the elevated plus maze and marble burying tests, enhanced acoustic startle response and impaired spatial memory retention while females were unaffected. SPS exposure did not alter auditory fear memory dynamics in males, but it did alter extinction retrieval in females. We provide the first evidence that SPS reproduces long-term emotional alterations in male, but not in female, rats which were observed 30 days following trauma exposure, thus resembling some of the hallmark symptoms of PTSD. Furthermore, our results show for the first time a long-term SPS-induced alteration of cued fear extinction in females. Our findings are relevant to future research on trauma-related disorders and may help develop sex-specific interventions to treat PTSD.

Combination of Stressors in the Critical Periods of Development Increases Resistance to Inflammatory Pain Stress in Adult Rats

We report here studies of the long-term effects of combined stress in the prenatal and prepubertal periods of development on measures of tonic inflammatory pain in the formalin test and the severity of depression-like behavior, and also the stress reactivity of the hormonal response in adult rats. In addition, the effects of the serotonin (5-HT) reuptake inhibitor fluoxetine and the 5-HT1A receptor agonist buspirone, given chronically to stressed mothers during pregnancy, on various types of adaptive behavior impaired by prenatal stress were assessed in rats of both sexes. The results showed that in rats of both sexes prenatal stress increased the pain response organized at the spinal and supraspinal levels of the central nervous system and that fluoxetine and buspirone normalized responses. Stress during the prepuberal period of development eliminated the effects of prenatal stress on the inflammatory pain responses integrated at the supraspinal level in adult rats; in these conditions, fluoxetine and buspirone had no effects, in contrast to their antinociceptive actions on the pain response integrated at the spinal level. Stress at prepubertal age eliminated sex-related differences seen in depression-like behavior in prenatally unstressed and prenatally stressed rats given physiological saline. Control adult females and adult females exposed to prenatal stress in the prepubertal period showed increases in the plasma corticosterone level after forced swimming as compared with the basal hormone level, though there were no significant differences in the level of stress reactivity of the hormonal response after forced swimming. Thus, the conditions for stress actions increasing stress resistance in adult rats were identified. Stress in the critical period of development formed a phenotype with increased stress resistance to inflammatory pain, which was seen in responses organized at the supraspinal level in adult individuals.

Early postnatal stress impairs insulin secretion in response to psychological stress in adult rats.

Adversity in early life can induce metabolic defects in exposure to stress in adulthood. Therefore, the exploration of involving mechanisms can be helpful in the treatment of metabolic disorders. So, the present study was conducted in terms of exploring the effects of interaction between early postnatal stress and young adulthood psychological stress on insulin secretion and pancreatic GLUT-2 levels in male rats. Footshock as a model of early life stress (at 2weeks of age) and psychological stress induced by communication box as a model of young adulthood stress (at 8-10weeks of age) were induced in male Wistar rats for five consecutive days (2times/day). Blood samples were drawn to measure glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell dysfunction (HOMA-B), before and after stress protocol in young adult rats. Corticosterone was measured on days 1 and 5 of stress induction. The day after the stress period, factors including glucose tolerance, TNF-alpha, isolated islets' insulin output and levels of pancreatic GLUT-2 protein via western blotting were determined. The combination of early footshock exposure and psychological stress during adulthood did not affect plasma corticosterone, but increased plasma insulin, HOMA-IR, HOMA-B and TNF-alpha levels. Plasma TNF was not only increased by the combination of both stressors, but also after only E STR exposure. HOMA-IR was increased in both Psy STR and E + Psy-STR groups. Plasma glucose just increased in Psy STR group. The combination of these two life stressors further increased the in vitro insulin secretion from isolated islets in response to 16.7-mM glucose. The level of Glut2 was increased in Psy STR and decreased in both E STR and E + Psy STR groups. Finally, glucose tolerance was impaired and glucose-stimulated insulin secretion was increased in E + Psy STR group. In conclusion, inducing stress in early life makes the organism more susceptible to metabolic defects in exposure to psychological stress later in life.

SAT-451 Chronic Stress During Adolescence of Rats Shows Sex Dimorphism in the Thyroid Axis Response to Voluntary Exercise in Adulthood

Exposure to chronic stress during adolescence causes long-term effects on the response of Hypothalamus-Pituitary-Adrenal (HPA) axis, affecting behavior and energy homeostasis. Voluntary exercise activates the HP-Thyroid (HPT) axis allowing efficient fluxes of substrates to active target organs. Chronic stress in adult rats blunts HPT axis response to voluntary exercise in a sex-dependent manner (Front Endocrinol 10(418):1-13, 2019). As adolescents show sex-dependent responses to stress, we sought to evaluate the effect of chronic stress at this period in the response of HPT axis to voluntary exercise in adulthood. Wistar male and female rats were divided in an undisturbed group (Control, C) and one group exposed to chronic variable stress (CVS) where the rats were daily subjected to different stressors during postnatal day (PND) 30 to 60 for females and PND 30 to 70 for males. At adulthood (PND 74 for females and PND 84 for males) rats were exposed to running wheel following published protocol (Endocrinology 155:2020-2030, 2014). As females are more susceptible to stress during adolescence than males, additional independent experiments were performed with female rats kept in group or individual housing, since PND 30 (2 per cage or isolated (Iso)). At PND 64, Iso rats were housed in pairs and exposed to CVS every 3 days until PND 80; later, rats were exercised 26 days. Hormones were quantified by ELISA or RIA; mRNA expression was determined by RT-PCR. Voluntary exercise reduced fat mass in C groups, dependent on the amount of exercise performed; stressed rats exercised did not lose fat, indicating that adolescent stress avoids an appropriate energy distribution during exercise. The expression of Crh and Avp in hypothalamic paraventricular nucleus (PVN) decreased in stressed groups mainly in females, as reported. Exercise decreased corticosterone levels only in C rats, suggesting that CVS during adolescence modifies the HPA axis response to exercise. CVS inhibited Pomc expression induced by exercise and increased Npy expression in arcuate nucleus, decreased Trh expression in PVN for both sexes and in dorsomedial hypothalamus in males. Thyroid hormones were not altered in CVS males and Iso females; however, T3 and T4 levels were high in CVS females, so different stress exposures may modify the HPT axis state in females. The response to exercise of the target organs of thyroid hormones reveals with more accuracy the activity of HPT axis, exercise stimulated the expression of Adrb3 and Dio2 in brown adipose tissue of C females, and the expression of Dio2 and Pgc1a in skeletal muscle (gastrocnemius) of both sexes, changes attenuated by CVS. These results indicate that chronic stress during adolescence blunts the response of HPT axis to voluntary exercise, strongly in females than males.

Сочетание стрессовых воздействий в критические периоды развития повышает устойчивость к стрессу воспалительной боли у взрослых крыс

We studied the long-term effect of the combination of stress in the prenatal and prepubertal periods of development on indicators of tonic inflammatory pain in the formalin test and the depressive-like behavior, as well as on the stress reactivity of the hormonal response in adult rats. In addition, in rats of both sexes, the effect of serotonin reuptake inhibitor (5-HT) fluoxetine and 5-HT1A agonist buspirone, chronically administered to their stressed mothers during pregnancy, on the studied types of adaptive behavior disturbed by prenatal stress was evaluated. It was found that in rats of both sexes, prenatal stress intensified the pain response organized at the spinal and supraspinal levels of the central nervous system, fluoxetine and buspirone normalized them. Stress in the prepubertal period of development leveled the effect of prenatal stress on the inflammatory pain response integrated at the supraspinal level in adult rats; under these conditions, fluoxetine and buspirone did not act, unlike their antinociceptive effect on the pain response integrated at the spinal level. Stress in prepubertal age leveled the sex differences found in the depressive-like behavior in prenatally non-stressed and prenatally stressed rats with saline. In control adult females and adult females with prenatal effects, prepubertal stress increased plasma corticosterone after forced swimming compared to basal hormone levels, but no significant differences in the level of stress reactivity of the hormonal response after forced swimming were found. Thus, the conditions of stressful impacts that increase resistance to stress in adult rats are identified. Stress in critical periods of development forms a phenotype with increased stress resistance to inflammatory pain, which was found in the response organized at the supraspinal level in adults.

Protective Effect of Hydroalcoholic Extract of Solanum surattense on Brain Tissue Damage and Oxidative Stress in Adult Rats with Toxoplasmosis

Introduction: Toxoplasmosis is caused by a protozoan named Toxoplasma gondii. This protozoan is a parasite of cats that can spread among other animals and birds around the world and cause a disease that varies from mild to severe. The disease is seen in the forms of acquired toxoplasmosis and congenital toxoplasmosis. Many studies have shown that there is a relationship between reproductive function and toxoplasmosis. T. gondii has led to decreased reproductive performance of males and females in many experimental animals. The aim of this study was to investigate the protective effect of hydroalcoholic extract of Solanum surattense on the brain tissue damage and brain oxidative stress induced by T. gondii in adult rats. Methods: For this purpose, 32 adult female rats were randomly divided into 4 groups. In group 1, 8 healthy rats received IP saline for 3 weeks. In group 2, 8 rats with T. gondii received IP saline for 3 weeks. In group 3, 8 rats with T. gondii received the hydroalcoholic extract of S. surattense for 3 weeks. In group 4, 8 healthy rats received the hydroalcoholic extract of S. surattense for 3 weeks. Then, brain tissue resection was performed to evaluate histological damage and levels of antioxidant enzymes. Results: Histological and biochemical studies showed that T. gondii had a deleterious effect on the brain tissue of rats and increased the level of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The administration of hydroalcoholic extract of S. surattense improved these effects due to its high antioxidant properties. Conclusion: The administration of the appropriate dose of hydroalcoholic extract of S. surattense for three consecutive weeks had a protective effect on brain tissue exposed to T. gondii.

Role of Angiotensin II in Cardiovascular Stress Responses in Rats Exposed to Glucocorticoids in Utero

It is well known that even transient prenatal insults can impact cardiovascular function in adulthood. We have hypothesized that adult cardiovascular disease may have its origins in utero as a result of exposure to elevated levels of glucocorticoids. In support of this, we have shown that when pregnant rat dams are treated with the glucocorticoid, dexamethasone (DEX), for the last 4 days of gestation, female‐specific changes resulting in autonomic dysfunction and enhanced pressor and tachycardic responses to stress are detected in their adult offspring. Given the known role of angiotensin II in influencing the autonomic nervous system, the present study investigated the impact of angiotensin receptor antagonism on the cardiovascular stress responses in adult male and female rats that were exposed to DEX in utero. Pregnant dams were administered DEX (0.4 mg/kg per day, s.c.) or vehicle on gestation days 18–21. This resulted in a significant reduction in birthweight in DEX‐exposed males and females. At 2–3 months of age, arterial pressure was assessed via radiotelemetry. In order to assess whether prenatal DEX alters stress‐induced hypertensive and tachycardic responses, rats were placed in a restraint tube for 20 minutes, followed by a 2hr recovery period. Restraint‐stress testing was performed on diestrus in females. Restraint stress was then repeated following a 5‐day treatment with the angiotensin type 1 receptor antagonist, losartan (30 mg/kg per day, i.p). In female offspring, prenatal exposure to DEX resulted in enhanced elevations in systolic and diastolic pressure as well as heart rate in response to restraint stress relative to vehicle‐exposed rats. Treatment with losartan reduced the pressor and tachycardic responses to restraint, only in female rats that were prenatally exposed to DEX. In male rats, neither in utero exposure to DEX, nor losartan treatment altered the pressor or tachycardic response to stress in adult rats. These findings suggest that prenatal programming of cardiovascular disease due to exposure to glucocorticoids may be mediated in part due to long‐term changes in the renin angiotensin system, and this effect may be sex‐specific.Support or Funding InformationABRC ADHS14‐082990This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Immediate and late effects of chronic stress in the testes of prepubertal and adult rats.

The objective of this study was to investigate the effects of chronic stress on the testes of prepubertal and adult rats and to evaluate whether any alterations could be reversed when stress induction is ended. Seventy-six male rats were assigned to eight groups depending on the type of treatment (control or stressed), the age at which stress was initiated (prepubertal or adult), and the time of evaluation (immediate or late). Stress stimuli were applied for 6 weeks. Stressed prepubertal and adult rats evaluated immediately after the last stress stimulus were included in SP-I and SA-I groups, respectively. The late prepubertal (SP-L) and adult (SA-L) groups of stressed rats were evaluated 6 weeks after the last stress stimulus. Age-matched rats were used as controls (CP-I, CA-I, CP-L, and CA-L groups). Application of stress stimuli to rats in the SP-I group resulted in body weight and seminiferous tubule diameter reduction. The rats in the SA-I group also showed several functional (testosterone level and sperm parameter) and morphological (testicular weight and seminiferous tubule diameter) reductions. The rats in the SP-L group showed increased body weight and intertubular compartment volumetric and absolute densities and reduced tubular compartment volumetric density. The rats in the SA-L group presented only reduced sperm viability. Stress stimuli promoted changes in the rats in all the study groups. The testes of the adult rats were the most affected by chronic stress. However, the stressed adult rats recovered well from the testicular alterations.

Effect of adiantum capillus veneris against irradiation-induced oxidative stress in adult rats

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues.