Adrenal Weight Research Articles

INTERSTRAIN DIFFERENCES IN EMOTIONAL AND WEIGHT INDICES IN GC RATS WITH CATATONIC RESPONSE AND WISTAR RATS

In selecting rats for behavior, we observe a direct natural effect and affect the nonspecific stress function. In this process, new behavioral phenotypes appear in the strain under selection. They differ from the selected forms in the selection criterion. In the GC strain, a large proportion of the so-called nervous rats emerge. The criterion presumes the selection for the long cataleptic freezing character, whereas the nervous rats display elevated motor excitement: running, jumping, and vocalization. The main purpose of our study was to assess phenotypic indices in GC rats (abbreviated from genetic and catatonia) and recognize principal components of variability for emotional and weight indices. Rats of the ancestral Wistar population were taken as control. The following indices were measured: time of cataleptic freezing, excitement level, blood pressure, acoustic startle response, seizure activity, and weights of the heart, kidneys, adrenals, and spleen. Multivariate analysis methods were applied: factor analysis and principal component analysis. We confirmed the inclination of GC rats of the generation studied to freezing in quiet surrounding and after a strong acoustic sti - mulus. More pronounced startle responses, moderate hypertension, and larger weights of the heart and adrenals were noted. Two principal variability components were recognized: startle amplitude (PC1) and morphofunctional variability (PC2). The figure shows different locations of Wistar and GC individuals in principal component coordinates. The principal component method confirmed the genetic relationship between the startle and nervousness responses. It was shown that in PC2 the indices of heart, kidney, adrenal, and spleen weight exert negative effects, whereas the effects of startle and nervousness were positive. In the same component, an increase in the startle and nervousness responses positively correlates with the relative weights of the heart and adrenals. Differences in the directions of the contributions to the second component of morphofunctional variability are discussed.

Intermittent hypoxia improves behavioral and adrenal gland dysfunction induced by posttraumatic stress disorder in rats.

Nonpharmacological treatments of stress-induced disorders are promising, since they enhance endogenous stress defense systems, are free of side effects, and have few contraindications. The present study tested the hypothesis that intermittent hypoxia conditioning (IHC) ameliorates behavioral, biochemical, and morphological signs of experimental posttraumatic stress disorder (PTSD) induced in rats with a model of predator stress (10-day exposure to cat urine scent, 15 min daily followed by 14 days of stress-free rest). After the last day of stress exposure, rats were conditioned in an altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5. PTSD was associated with decreased time spent in open arms and increased time spent in closed arms of the elevated X-maze, increased anxiety index, and increased rate of freezing responses. Functional and structural signs of adrenal cortex degeneration were also observed, including decreased plasma concentration of corticosterone, decreased weight of adrenal glands, reduced thickness of the fasciculate zone, and hydropic degeneration of adrenal gland cells. The thickness of the adrenal fasciculate zone negatively correlated with the anxiety index. IHC alleviated both behavioral signs of PTSD and morphological evidence of adrenal cortex dystrophy. Also, IHC alone exerted an antistress effect, which was evident from the increased time spent in open arms of the elevated X-maze and a lower number of rats displaying freezing responses. Therefore, IHC of rats with experimental PTSD reduced behavioral signs of the condition and damage to the adrenal glands. NEW & NOTEWORTHY Intermittent hypoxia conditioning (IHC) has been shown to be cardio-, vaso-, and neuroprotective. For the first time, in a model of posttraumatic stress disorder (PTSD), this study showed that IHC alleviated both PTSD-induced behavioral disorders and functional and morphological damage to the adrenal glands. Also, IHC alone exerted an antistress effect. These results suggest that IHC may be a promising complementary treatment for PTSD-associated disorders.

Effects of Prior Psychosocial Trauma on Subsequent Immune Response After Experimental Thorax Trauma.

Overshooting inflammation during the early phase after blunt thorax trauma promotes the development of acute respiratory distress syndrome, multiple organ failure, and subsequent mortality. Given that individuals diagnosed with stress-related disorders are characterized by chronic low-grade inflammation, we hypothesize that "psychosocial traumatic preload" poses a risk factor for the abovementioned complications after thorax trauma.Here, we used the chronic subordinate colony housing (CSC) paradigm to induce "psychosocial traumatic preload" and systemic low-grade immune activation in male mice, indicated by elevated plasma concentrations of different inflammatory mediators. Subsequent thorax trauma was induced in anaesthetized mice by a single blast wave centered on the thorax; SHAM animals were exposed to anesthesia only. Mice were killed 2, 6, and 24 h after thorax trauma or SHAM treatment.Independent of thorax trauma, CSC caused an increase in adrenal weight, and a decrease in thymus weight, indicating that the stress paradigm worked reliably. Moreover, although lung histology was not affected by prior stress, CSC exposure aggravated the early immune response after thorax trauma, indicated by elevated myeloperoxidase lung concentrations in thorax trauma-exposed CSC versus respective single-housed control (SHC) mice (2 h). Furthermore, thorax trauma caused an increase in total bronchoalveolar lavage fluid (BAL) protein (24 h), BAL C5a (2 h), BAL cell counts (24 h), and BAL keratinocyte chemoattractant (6 h and 24 h) in CSC but not SHC mice.Our data indicate that repeated psychosocial traumatization during adulthood moderately aggravates the local immune response toward thorax trauma, but overall may be considered as a rather minor risk factor in terms of thorax trauma-associated complications.

Perinatal and long-term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth-restricted guinea pig fetus.

Uterine artery application of adenoviral vascular endothelial growth factor A165 (Ad.VEGF-A165) gene therapy increases uterine blood flow and fetal growth in experimental animals with fetal growth restriction (FGR). Whether Ad.VEGF-A165 reduces lifelong cardiovascular disease risk imposed by FGR remains unknown. Here, pregnant guinea pigs fed 70% normal food intake to induce FGR received Ad.VEGF-A165 (1×1010 viral particles, n = 15) or vehicle ( n = 10), delivered to the external surface of the uterine arteries, in midpregnancy. Ad libitum-fed controls received vehicle only ( n = 14). Litter size, gestation length, and perinatal mortality were similar in control, untreated FGR, and FGR+Ad.VEGF-A165 animals. When compared with controls, birth weight was lower in male but higher in female pups following maternal nutrient restriction, whereas both male and female FGR+Ad.VEGF-A165 pups were heavier than untreated FGR pups ( P < 0.05, ANOVA). Postnatal weight gain was 10-20% greater in female FGR+Ad.VEGF-A165 than in untreated FGR pups, depending on age, although neither group differed from controls. Maternal nutrient restriction reduced heart weight in adult female offspring irrespective of Ad.VEGF-A165 treatment but did not alter ventricular wall thickness. In males, postnatal weight gain and heart morphology were not affected by maternal treatment. Neither systolic, diastolic, mean arterial pressure, adrenal weight, nor basal or challenged plasma cortisol were affected by maternal undernutrition or Ad.VEGF-A165 in either sex. Therefore, increased fetal growth conferred by maternal uterine artery Ad.VEGF-A165 is sustained postnatally in FGR female guinea pigs. In this study, we did not find evidence for an effect of maternal nutrient restriction or Ad.VEGF-A165 therapy on adult offspring blood pressure.

Functional disruption of stress modulatory circuits in a model of temporal lobe epilepsy.

Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy-related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e. social estrangement, employment changes) is not clear. Animal models provide an opportunity to dissociate these factors. Therefore, we queried whether epileptic mice would reproduce neuroendocrine and behavioral changes associated with human epilepsy. Male FVB mice were exposed to pilocarpine to induce status epilepticus (SE) and the subsequent development of spontaneous recurrent seizures. Morning baseline corticosterone levels were elevated in pilocarpine treated mice at 1, 7 and 10 weeks post-SE relative to controls. Similarly, epileptic mice had increased adrenal weight when compared to control mice. Exposure to acute restraint stress resulted in hypersecretion of corticosterone 30 min after the onset of the challenge. Anatomical analyses revealed reduced Fos expression in infralimbic and prelimbic prefrontal cortex, ventral subiculum and basal amygdala following restraint. No differences in Fos immunoreactivity were found in the paraventricular nucleus of the hypothalamus, hippocampal subfields or central amygdala. In order to assess emotional behavior, a second cohort of mice underwent a battery of behavioral tests, including sucrose preference, open field, elevated plus maze, 24h home-cage monitoring and forced swim. Epileptic mice showed increased anhedonic behavior, hyperactivity and anxiety-like behaviors. Together these data demonstrate that epileptic mice develop HPA axis hyperactivity and exhibit behavioral dysfunction. Endocrine and behavioral changes are associated with impaired recruitment of forebrain circuits regulating stress inhibition and emotional reactivity. Loss of forebrain control may underlie pronounced endocrine dysfunction and comorbid psychopathologies seen in temporal lobe epilepsy.

The Lateral Habenula Directs Coping Styles Under Conditions of Stress via Recruitment of the Endocannabinoid System

BackgroundThe ability to effectively cope with stress is a critical determinant of disease susceptibility. The lateral habenula (LHb) and the endocannabinoid (ECB) system have independently been shown to be involved in the selection of stress coping strategies, yet the role of ECB signaling in the LHb remains unknown. MethodsUsing a battery of complementary techniques in rats, we examined the localization of type-1 cannabinoid receptors (CB1Rs) and assessed the behavioral and neuroendocrine effects of intra-LHb CB1R manipulations. We further tested the extent to which the ECB system in the LHb is impacted following chronic unpredictable stress or social defeat stress, and whether manipulation of LHb CB1Rs can bias coping strategies in rats with a history of chronic stress. ResultsElectron microscopy studies revealed CB1R expression on presynaptic axon terminals, postsynaptic membranes, mitochondria, and glial processes in the rat LHb. In vivo microdialysis experiments indicated that acute stress increased the amount of 2-arachidonoylglycerol in the LHb, while intra-LHb CB1R blockade increased basal corticosterone, augmented proactive coping strategies, and reduced anxiety-like behavior. Basal LHb 2-arachidonoylglycerol content was similarly elevated in rats that were subjected to chronic unpredictable stress or social defeat stress and positively correlated with adrenal weight. Finally, intra-LHb CB1R blockade increased proactive behaviors in response to a novel conspecific, increasing approach behaviors irrespective of stress history and decreasing the latency to be attacked during an agonistic encounter. ConclusionsAlterations in LHb ECB signaling may be relevant for development of stress-related pathologies in which LHb dysfunction and stress-coping impairments are hallmark symptoms.

Adrenal Gland of the Adult female Duck (Anas platyrhynchos)

The aim of this study was to investigate the morphological&amp; histological properties of the female Duck (Anas platyrhynchos) adrenal gland in babilon.For this purpose, ten adrenals were collected from five adult female ducks.The ducks have paired glands located in the abdominal cavity at the anterior end of the kidneys.The shape of right gland is semi-circularwhile the left elongated or triangular in shape. The mean weight of the right adrenal gland of duck was 0.39g while the left was o.41g. The relative volume of the components remained essentially the same in both glands. The mean values of long axis of left adrenal gland 15.46mm and the diameter of right gave mean values 11.30mm.The adrenal cortex is subdivided into three zones. The outermost zone was formed as zona glomerulosa. It contained prismatic cells that formed irregular clusters or cords and contained lipid vacuoles. The second zone is zona fasciculata appeared foamy. The zona reticularis appeared as irregular cords and smaller than other two zones of cortex. Medulla. The adrenal medulla was about one quarter of the area of the gland. The chromaffin cells in irregular clusters,. Epinephrine-storing cells (E-cells) were more numerous and smaller than norepinephrine-storing cells (NE-cells). Both chromaffin cells contained a single large spherical nucleus

Long‐term Somatic Hypoalgesia as a Marker of Pathological Conditions in Gastrointestinal Tract

Pain is traditionally considered as an evolutionarily developed defensive response to noxious stimulus. Short‐term pain suppression in response to stressful factors (stress‐induced analgesia) is an important adaptive reaction that is required for survival if further injury or death were threatened. In contrast, long‐term pain suppression may be considered as a sign of pain abnormality induced by disturbance of endogenous pain mechanisms under circumstances of pathology. Indomethacin (IM) is commonly used in clinic; however, it has a side ulcerogenic effect on the gastrointestinal tract. Previously we have shown that the formation IM‐induced injury in gastrointestinal tract is accompanied by a decrease in somatic pain sensitivity lasting, a least, for 72 h after IM injection (long‐term somatic hypoalgesia). Here we tested hypothesis that suppression of pathological process in gastrointestinal tract may prevent somatic hypoalgesia and normalize pain regulation in conscious rats. For this we studied effects of “stress preconditioning” on the gastrointestinal tract and somatic pain sensitivity under circumstances of ulcerogenic action of IM (35 mg/kg, sc). Preliminary (24 h) fasted rats were subjected one of four exposures (“stress preconditioning”) before IM administration: a) cold restraint (30 min, t=10 degree C, 1 h before IM); b) CRF (1.25 mkg/kg, ip, 30 min before IM) administration; c) capsaicin (0.5/kg, sc, 1 h before IM) administration, d) forced treadmill running (30 min, 1 h before IM). Pain sensitivity was assessed by tail flick latencies (tail flick test) or number of pain responses induced by acetic acid (“writhing test”). IM administration caused the formation of gastric erosion (2–4 h after injection) and small intestine injury (24, 48, 72 h after injection) that was accompanied by an increase in tail flick latencies (long‐term somatic hypoalgesia). Somatic hypoalgesia 48 h after IM injection was also supported by a decrease in number of pain responses induced by acetic acid. IM‐induced pathological process in the gastrointestinal tract was followed by changes in plasma corticosterone levels, cardiovascular (heart rate, blood pressure) and somatic (weights of thymus and adrenals, body weight) parameters. Each preconditioning exposure attenuated IM‐induced gastric mucosa injury and prevented somatic hypoalgesia. The results obtained suggest that long‐term somatic hypoalgesia may be one of characteristics of pathological process in the gastrointestinal tract induced by ulcerogenic action of IM.Support or Funding InformationThe study was supported by grant of Russian Science Foundation (RSF) №14‐15‐00790.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Paternal physical exercise demethylates the hippocampal DNA of male pups without modifying the cognitive and physical development

Maternal exercise is known to have beneficial effects in progeny development, but the influence of paternal exercise on the offspring still unclear. Since spermatogenesis is a continuous process, the father’s life experiences can reprogram epigenetic content of the sperm and somehow interfere on offspring phenotype. This study was designed to evaluate the effects of paternal physical exercise on cognitive and physical development and on hippocampal DNA methylation levels of the offspring. Adult male Wistar rats were divided into two groups: sedentary and exercised. The exercise protocol occurred before mating and consisted of treadmill running, 5 consecutive days/week for 8 weeks (20 min/day). The mothers were not trained. The following developmental parameters were examined in male offspring: body growth, physical and cognitive performance, weights of adrenal glands, gonadal fat and hindlimb muscles, BDNF expression and global DNA methylation at the hippocampus. The progeny of trained and sedentary fathers did not differ in relation to physical parameters and performance, spatial memory and BDNF expression. However, paternal exercise promoted a decrease in offspring´s relative gonadal fat weight and a lower percentage of global hippocampal DNA methylation compared to offspring of sedentary fathers. These results pointed to interference of male physical activity at the time of conception on adiposity and hippocampal epigenetic reprogramming of male offspring. The data reinforces that exercise does not harm the descendant’s development and emphasize the benefits to include the practice of physical exercise in a healthier lifestyle of the parents. Nevertheless, future studies are necessary and should investigate further the long-effects of epigenetic mechanisms in order to elucidate the father’s contribution in fetal programming.

Ventral tegmental area inactivation alters hormonal, metabolic, and locomotor responses to inescapable stress

Context: The involvement of unilateral and bilateral inhibition of the ventral tegmental area (VTA) in response to stress is not well understood.Objective: In the present study, the effect of unilateral and bilateral inhibition of the VTA on hormonal, metabolic, and locomotor responses to stress was assessed.Material and methods: Male rats seven days after cannulation into the VTA received electro foot-shock stress for seven consecutive days. Twenty minutes before induction of stress, 2% lidocaine hydrochloride or sterile saline (control) was injected either uni- or bi-laterally into the VTA.Results: Results showed that stress significantly increased serum corticosterone level, adrenal gland weight and anorexia, reduced weight gain, food-intake, and locomotor activity. However, bilateral inactivation of VTA prevented stress-induced these parameters changes.Conclusion: The present study demonstrated that the bilateral VTA blockade effectively relieves the symptoms of stress, while the unilateral VTA blockade does not significantly improve the changes caused by stress.

Evaluation of subchronic exposure to triclosan on hepatorenal and reproductive toxicities in prepubertal male rats

ABSTRACTTriclosan (TCS), a common antimicrobial ingredient, is present in many consumer products, including soaps, shampoos, and toothpaste. Owing to its widespread use, potential adverse effects on animals and humans may arise from lifetime exposure, but data on chronic prepubertal exposure of TCS are still lacking. The aim of the present study was to investigate the influence of subchronic TCS exposure (0.25, 25, 250, or 750 mg/kg) on target organ toxicity in prepubertal male rats. After daily administration of TCS to rats by oral gavage for 60 d, a significant reduction in body weight and relative weights of liver, kidneys, testes, and adrenal glands was observed in the 750-mg/kg (high dose) group. Serum alanine aminotransferase and aspartate aminotransferase activities as well as levels of blood urea nitrogen, and creatinine were significantly increased at 750 mg/kg TCS. Further, TCS (750 mg/kg) elevated the protein expressions of hepatic CYP2B1, RXR/PPAR, and levels of malondialdehyde. High-dose TCS exposure induced histological changes as evidenced by reduction of Bowman’s space, occlusion of the tubular lumen, and degeneration of tubular epithelial cells in the kidney. Tubular necrosis was confirmed as evidenced by a rise in expression of high mobility group box 1 renal protein. Daily sperm production was significantly diminished by high doses of TCS with marked inhibition of androgen receptor protein expression. Our results indicated that subchronic exposure to excessively high concentrations of 750 mg/kg TCS induced hepatorenal and reproductive toxicities in prepubertal male rats; however, the biological relevance of these findings is questionable as these drug levels are not encountered in the environment.

Transgenerational effects of polychlorinated biphenyls: 1. Development and physiology across 3 generations of rats

BackgroundPolychlorinated biphenyls (PCBs) are persistent organic environmental contaminants and known endocrine-disrupting chemicals (EDCs). Previous studies demonstrated that developmental exposure to the weakly estrogenic PCB mixture Aroclor 1221 (A1221) in Sprague-Dawley rats altered sexual development, adult reproductive physiology and body weight. The current study tested the hypothesis that prenatal A1221 exposure not only disrupts these endpoints within an exposed individual’s (F1 generation) lifespan, but may also affect subsequent generations (F2-F3).MethodsWe treated pregnant female rats on embryonic days (E) 16 and E18 with A1221 (1 mg/kg), estradiol benzoate (50 μg/kg, positive estrogenic control), or vehicle (3% DMSO in sesame oil, negative control). Endpoints related to sexually dimorphic developmental trajectories of reproductive and developmental physiology were measured, and as adults, reproductive endocrine status was assessed, in the F1, F2, and F3 generations.ResultsSignificant effects of transgenerational EDCs were found for body weight and serum hormones. The A1221 descendants had significantly higher body weight in the F2-maternal lineage throughout postnatal development, and in F3-maternal lineage animals after weaning. In females, generation- and lineage-specific effects of exposure were found for serum progesterone and estradiol. Specifically, serum progesterone concentrations were lower in F2-A1221 females, and higher in F3-A1221 females, compared to their respective F2- and F3-vehicle counterparts. Serum estradiol concentrations were higher in F3-A1221 than F3-vehicle females. Reproductive and adrenal organ weights, birth outcomes, sex ratio, and estrous cycles, were unaffected. It is notable that effects of A1221 were only sometimes mirrored by the estrogenic control, EB, indicating that the mechanism of action of A1221 was likely via non-estrogenic pathways.ConclusionsPCBs caused body weight and hormonal effects in rats that were not observed in the directly exposed F1 offspring, but emerged in F2 and F3 generations. Furthermore, most effects were in the maternal lineage; this may relate to the timing of exposure of the F1 fetuses at E16 and 18, when germline (the future F2 generation) epigenetic changes diverge in the sexes. These results showing transgenerational effects of EDCs have implications for humans, as we are now in the 3rd generation since the Chemical Revolution of the mid-twentieth century, and even banned chemicals such as PCBs have a persistent imprint on the health of our descendants.

Lifelong Aerobic Exercise Reduces the Stress Response in Rats

The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic–pituitary–adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system.AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease.

Ovine uteroplacental and fetal metabolism during and after fetal cortisol overexposure in late gestation.

Cortisol modifies fetal metabolism in preparation for delivery, but whether preterm cortisol exposure programs persisting changes in fetoplacental metabolism remains unknown. This study infused fetal sheep with saline (n = 36) or cortisol (n = 27) to raise fetal plasma cortisol to normal prepartum concentrations for 5 days from day 125 of gestation (term: ≈145 days). Fetal uptake and uteroplacental metabolism of glucose, oxygen, and lactate, together with fetal hepatic glucogenic capacity, were measured on the final day of infusion or 5 days later. Cortisol reduced adrenal weight and umbilical glucose uptake during infusion but increased fetal glucose concentrations, hepatic glycogen content, and hepatic glucogenic enzyme activity (fructose-1,6-bisphosphatase and glucose-6-phosphatase) and gene expression (PC and G6PC) compared with saline infusion. Postcortisol infusion, umbilical glucose uptake, and hepatic glucose-6-phosphatase activity remained low and high, respectively, whereas fetal glucose levels normalized and hepatic glycogen was lower with higher adrenal weights than in controls. Cortisol infusion increased the proportion of total uterine glucose uptake consumed by the uteroplacental tissues, irrespective of age. Placental tracer glucose transport capacity was also increased after, but not during, cortisol infusion, without changes in placental glucose transporter gene expression. Blood lactate concentration and Pco2 were higher, whereas pH and O2 content were lower in cortisol-infused than saline-infused fetuses, although uteroplacental metabolism and fetal uptake of oxygen and lactate were unaltered. The results suggest that preterm cortisol overexposure alters fetoplacental metabolism and adrenal function subsequently with persisting increases in uteroplacental glucose consumption at the expense of the fetal supply.

The Pyramid Counteracts Chronic Prenatal Restraint-Stress Effects on the Milestones, Anthropometry, and Body, Brain and Adrenal Gland Weights of Pups in Rats

Prenatal exposure to chronic stress during critical periods of foetal development produces depression, attention and learning deficits, hormonal imbalances and affects the brain. The effect of prenatal restraint-stress on the postnatal developmental milestones, anthropometric measurements, and the body, brain and adrenal gland weights of the pups were examined and compared with the un-restrained control and the restrained group under the pyramid at postnatal day 10 and 21. Pregnant rats were restrained (9h/day) from gestation day 7 until parturition. Results showed significant delay in the milestones by one day in the restraint control (RC) compared to the unrestrained normal control (NC), while pups of the restrained pyramid (RP) group did not show the delay. Significant decreases in the anthropometric measurements, body and brain weights in RC group were observed at both postnatal days, while the RP group results matched with the NC group. Significant increase in the adrenal weights was found in the RC group compared to NC group and not the RP group. Results suggest prenatal restraint-stress definitely hampers the developmental milestones, anthropometric measurements, and body and brain weights of the young offspring. Results suggest, pyramid environment counteracts and protects the deleterious effects of chronic prenatal stress. Keywords: Anthropometry, Milestones, Prenatal stress, Pyramid

Insights into the potential antidepressant mechanisms of cilostazol in chronically restraint rats: impact on the Nrf2 pathway.

Ample evidence has pointed to a close link between oxidative stress, mitochondrial dysfunction, and depression. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a master regulator of cellular redox homeostasis and affects mitochondrial function. Nrf2 holds promise for depression prevention and treatment. This study aimed to investigate the potential prophylactic antidepressant effect of cilostazol and the contribution of the Nrf2 pathway toward the putative neuroprotection. The behavioral and neurochemical effects of concomitant treatment of oral cilostazol at doses of 7.5, 15, and 30 mg/kg/day in Wistar rats exposed to chronic restraint stress (CRS) for 4 weeks were assayed. Cilostazol prevented CRS-induced depressive-like behavior shown in sucrose-preference, forced-swimming, and open-field tests, and hypothalamus-pituitary-adrenal axis hyperactivity (adrenal gland weight and serum corticosterone). Cilostazol prevented CRS-induced increase in hippocampal lipid peroxidation and 8-hydroxy-2'-deoxyguanosine, and a decrease in antioxidant activities (glutathione level, superoxide dismutase, and catalase). Western blot and PCR showed that cilostazol favorably modulated the Nrf2 protein and heme oxygenase-1 and NAD(P)H: quinone oxidoreductase-1 gene expression in the hippocampus of CRS rats. Cilostazol also prevented the decrease in the hippocampal activities of mitochondrial respiratory enzyme complexes I-IV. These behavioral and biochemical findings indicated the potential prophylactic antidepressant effect and mechanism of cilostazol by preventing oxidative stress by activation of redox defense mechanisms mediated through the Nrf2 pathway and restoring mitochondrial dysfunction.

Protective roles of Rutin against restraint stress on spermatogenesis in testes of adult mice.

In order to investigate the effects of Rutin against restraint stress, 50 adult male mice were divided into five groups: control, restraint stress (RS), and RS with 2 doses of Rutin treatments. Mice were restrained in a conical tube for 4 h daily and Rutin was injected intraperitoneally for 15 consecutive days. Restraint stress significantly decreases body weights, testis and epididymis weights, thymus weights, visceral fats, serum concentrations of testosterone, sperm counts, sperm motility and sperm viability, while it increases serum epinephrine levels, adrenal gland weights and abnormal sperms. In addition, restraint stress severely damages the testicular histoarchitecture and spermatogenesis. Stressed groups also showed broken seminiferous tubules, few spermatozoa in lumen, less population of Leydig cells between the interstitial spaces, spermiation arrest in stage I-III and degenerated population of round spermatids in the lumen; as well as missing cells in stages IV-VI. Furthermore, lumen sizes increased in stages VII, VIII, IX and X. Residual bodies increased in stages IV-VI, VII-VIII and vacuoles found in stages XI-XII after restraint stress. PARP1 signaling is involved in apoptosis. In this study, expressional levels of cleaved PARP1 and cleaved Caspase-3 are significantly increased in testes after restraint stress. We demonstrate that Rutin significantly ameliorates the side effects induced by restraint stress.

Bisphenol A stimulates adrenal cortical cell proliferation via ERβ-mediated activation of the sonic hedgehog signalling pathway

We previously demonstrated that prenatal exposure to bisphenol A (BPA) resulted in increased adrenal gland weight independent of changes in plasma ACTH levels in adult mouse offspring. This finding suggested that BPA exposure likely had a direct effect on adrenal development. Given that (1) sonic hedgehog (Shh) signaling is essential for adrenal development; (2) deletion of the Shh gene in mice results in adrenal hypoplasia; (3) BPA is known to signal through estrogen receptor β (ERβ); and (4) ERβ is highly expressed in adrenal glands; we hypothesized that BPA stimulates adrenal cell proliferation via ERβ-mediated activation of the Shh pathway. To test this hypothesis, the human adrenal cell line, H295A cells, was used as an in vitro model system. Our main findings were: (1) BPA increased cell number and protein levels of proliferating cell nuclear antigen (PCNA; a universal marker of cell proliferation), cyclin D1 and D2 (key proliferation factors), as well as Shh and its key transcriptional regulator Gli1; (2) cyclopamine, a Shh pathway inhibitor, blocked these stimulatory effects of BPA on cell proliferation; (3) BPA increased the nuclear translocation of ERβ; and (4) the ERβ-specific agonist DPN mimicked while the ERβ-specific antagonist PHTPP abrogated the stimulatory effects of BPA on cell proliferation and Shh signaling. Taken together, these findings demonstrate that BPA stimulates adrenal cell proliferation likely through ERβ-mediated activation of the Shh signaling pathway. Thus, the present study provides novel insights into the molecular mechanisms underlying our previously reported BPA-induced aberrant adrenal phenotype.

The potential benefit of combined versus monotherapy of coenzyme Q10 and fluoxetine on depressive-like behaviors and intermediates coupled to Gsk-3β in rats

As a part of the serotoninergic dysfunction implicated in neurobiology of depression, evidence has focused on serotonin (5-HT) receptors downstream signaling intermediates including glycogen synthase kinase-3β (GSK-3β), cAMP response element binding protein (CREB) and brain derived neurotrophic factor (BDNF). Our team previously reported that coenzyme Q10 (CoQ10) exerted antidepressant-like effect in rats exposed to chronic unpredictable mid stress (CUMS) via elevating serotonin levels. However, the effect of CoQ10 has not been elucidated in downstream signaling molecules mediating 5HT receptors' effect involved in depressive disorder hitherto. In the present study, we focused on 5-HT1A and 5-HT2A receptors (activation of 5-HT1A receptor and inhibition of 5-HT2A receptors reduce depressive like-behaviors). We investigated the role of these 5-HT receptors and their linked GSK-3β signaling intermediates as an underlying mechanism of CoQ10 as monotherapy or combined with fluoxetine, a selective serotonin reuptake inhibitor, to alleviate depressive-like phenotype. Effects of CoQ10 (100mg/kg/day) or/and fluoxetine (10mg/kg/day) were determined on 5-HT1A, 5-HT2A receptors mRNA expression, GSK-3β and phosphorylated (p)GSK-3β, CREB, pCREB and BDNF protein expression in rats subjected to CUMS for 6weeks. CUMS rats exhibited obvious depressive-like behaviors (anhedonia-like behavior, negative alterations in social interaction, open field and forced swimming tests) with increased corticosterone and adrenal glands weight, decreased hippocampal levels of pGSK-3β, pCREB and BDNF protein expressions. Additionally, they exhibited decreased hippocampal 5-HT1A and increased 5-HT2A receptor mRNA expression. CoQ10 or fluoxetine significantly attenuated the behavioral and neurochemical alterations in stressed rats with more significance with combined treatment. These findings imply that CoQ10 or/and fluoxetine attenuated CUMS-induced depressive-like behavior partly through modulating dysfunctional regulation of post-serotonergic receptor signaling pathway focusing on GSK-3β, CREB and BDNF.

Is immunosuppression, induced by neonatal thymectomy, compatible with poor reproductive performance in adult male rats?

With increasing knowledge that the immune system has a major impact on reproductive ‎health, the potential for cells arising in organs such as the thymus to alleviate oxidative stress ‎has been revealed. This study addresses the impact of neonatal thymectomy on male ‎reproductive function in pubertal and adult animals. Neonatal Sprague Dawley rats were allotted to four treatments consisting of fully thymectomized, partially thymectomized, intact, and sham-operated rats. Half of the rats in each treatment were sacrificed at 40 and the other half at 80days of age. Testicular volume, ventral prostate and spleen weight, several sperm attributes (concentration, motility, livability, membrane integrity, sperm penetration into mucus, total antioxidant capacity, mitochondrial dehydrogenase activity), plasma superoxide dismutase, glutathione, and testosterone level as well as fertility decreased in thymectomized rats. Adrenal gland weight, sperm malondialdehyde level, indices of oxidative stress, sperm abnormality, testicular and sperm lipid peroxidation, protein carbonylation, and sperm reactive oxygen species generation increased in thymectomized rats. In thymectomized rats, the testes contained high levels of malondialdehyde but low levels of glutathione and ferric-reducing antioxidant power. Epididymal sperm reactive oxygen species, blood lipid peroxidation, and oxidative stress indices ‎‎in blood and spermatozoa were highest in fully thymectomized, intermediate ‎in partially thymectomized, and lowest in both pubertal and mature control rats. Blood levels of superoxide dismutase, lipid peroxidation indices, and ‎testosterone, and mitochondrial adenosine triphosphate and ‎dehydrogenase activities in epididymal spermatozoa were lowest in fully thymectomized, ‎intermediate in partially thymectomized, and highest in both pubertal and mature control rats.‎ The data indicated that increased oxidative stress and mitochondrial dysfunction might play a role in the mechanism of immunosuppression-induced testicular and sperm abnormalities.