Juvenile social defeat stress exposure favors in later onset of irritable bowel syndrome-like symptoms in male mice

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder. Traumatic stress during adolescence increases the risk of IBS in adults. The aim of this study was to characterize the juvenile social defeat stress (SDS)-associated IBS model in mice. Juvenile mice were exposed to an aggressor mouse for 10 min once daily for 10 consecutive days. Behavioral tests, visceral sensitivity, immune responses, and fecal bacteria in the colon were evaluated in 5 weeks after SDS exposure. Social avoidance, anxiety- and depression-like behavior, and visceral hypersensitivity were observed. Juvenile SDS exposure significantly increased the number of 5-HT-containing cells and calcitonin gene-related peptide-positive neurons in the colon. The gut microbiota was largely similar between the control and juvenile SDS groups. The alterations in fecal pellet output, bead expulsion time, plasma corticosterone concentration, and colonic 5-HT content in response to restraint stress were exacerbated in the juvenile SDS group compared with the control group. The combination of juvenile SDS and restraint stress increased the noradrenaline metabolite 3-Methoxy-4-hydroxyphenylglycol (MHPG) content and MHPG/noradrenaline ratio in the amygdala when compared with restraint stress in control mice. These results suggest that juvenile SDS exposure results in later onset of IBS-like symptoms.

H3K27 Acetylation of SF1 in PBMC: A Biomarker for Adrenal Insufficiency of Steroid Synthesis in Male Offspring Induced by Prenatal Dexamethasone Exposure

Dexamethasone is widely used for treating pregnant diseases. However, lots of studies have confirmed that prenatal dexamethasone exposure (PDE) could increase the risk of offspring multiple diseases. The purpose of this study was to elucidate the intrauterine epigenetic mechanism of adrenal developmental programming, and to explore early warning marker in peripheral blood mononuclear cells (PBMC). We found the adrenal morphological and functional changes before and after birth in PDE male offspring rats, which were performed as the decreases of serum corticosterone concentration, steroidogenic acute regulatory (StAR) expression, histone 3 lysine 27 acetylation (H3K27ac) level of steroidogenic factor1 (SF1) promoter region and its expression; meanwhile, the expression of glucocorticoid receptor (GR) and histone acetylation enzyme 5 (HDAC5) in PDE male fetal rats were increased. In vitro, dexamethasone reduced the expression of SF1 and StAR, and cortisol production, but increased the expression of GR and HDAC5, the binding between GR and SF1 promoter region, and protein interaction between GR and HDAC5. GR siRNA or HDAC5 siRNA could reverse the above effects of dexamethasone. Furthermore, in vivo, we confirmed that H3K27ac level of SF1 promoter region and its expression in PBMC of PDE group were decreased before and after birth, showing a positive correlation with the same indexes in adrenal. Meanwhile, in clinical trials, we confirmed that H3K27ac level of SF1 promoter region and its expression were decreased after prenatal dexamethasone application in neonatal PBMC. In conclusion, PDE induced adrenal insufficiency of male offspring rats, which was related to activate adrenal GR by dexamethasone in uterus. The activated GR, on one hand, increased its direct binding to SF1 promoter region to inhibit its expression, on the other hand, up-regulated and recruited HDAC5 to decrease H3K27ac level of SF1 promoter region, and strengthened the inhibition of SF1 and subsequent StAR expression.

Prolonged Peripheral Immunosuppressive Responses as Consequences of Random Amphetamine Treatment, Amphetamine Withdrawal and Subsequent Amphetamine Challenges in Rats

Drug-induced immunosuppression may underline increased hypothalamic–pituitary–adrenal axis response to stress observed following chronic psychostimulant treatment. However, the consequences of random amphetamine (AMPH) treatment, withdrawal and AMPH challenge after withdrawal on the peripheral immunity and systemic corticosterone response are unknown. In this study, the total blood and spleen leukocyte, lymphocyte, T, B, NK, TCD4+/TCD8+ cell numbers and ratio, pro-inflammatory interferon gamma (IFN-γ), and anti-inflammatory interleukin-4 (IL-4) production, and plasma corticosterone concentration in Wistar rats were investigated after: chronic, random AMPH/SAL treatment alone (20 injections in 60 days, 1 mg/kg b.w., i.p.), AMPH/SAL withdrawal (for 20 consecutive days after random AMPH/SAL exposure) or AMPH/SAL challenge after withdrawal (single injection after the AMPH/SAL withdrawal phase). The results showed blood and spleen leukopenia, lymphopenia, lower blood production of IFN-ɤ, and increased plasma corticosterone concentration after the AMPH treatment, which were more pronounced in the AMPH after withdrawal group. In contrast, an increased number of blood NK cells and production of IL-4 after chronic, random AMPH treatment alone, were found. Blood AMPH-induced leukopenia and lymphopenia were due to decreased total number of T, B lymphocytes and, at least in part, of granulocytes and monocytes. Moreover, decreases in the number of blood TCD4+ and TCD8+ lymphocytes both in the AMPH chronic alone and withdrawal phases, were found.The major findings of this study are that AMPH treatment after the long-term withdrawal from previous random AMPH exposure, accelerates the drug-induced immunosuppressive and systemic corticosterone responses, suggesting prolonged immunosuppressive effects and an increase in incidence of infectious diseases. Graphical Abstract Prolonged peripheral immunosuppressive responses as consequences of random amphetamine…The results indicate that the chronic and random AMPH exposure alone and the acute (single injection) challenge of the drug after the withdrawal phase induced long-term immunosuppressive effects, which were similar to those occurring during the stress response, and sensitized the peripheral immunosuppressive and corticosterone responses of the rat to the disinhibitory effects of this stressor.

Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats

Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity.

Maternal behavior and the neonatal HPA axis in the Wistar Audiogenic Rat (WAR) strain: early life implications for a genetic animal model in epilepsy

Epileptogenesis is a multistage process and seizure susceptibility can be influenced by stress early in life. Wistar Audiogenic Rat (WAR) strain is an interesting model to study the association between stress and epilepsy, since it is naturally susceptible to seizures and present changes in the hypothalamus-pituitary-adrenal (HPA) axis activity. All these features are related to the pathogenic mechanisms usually associated to psychiatric comorbidities present in epilepsy. Therefore, the current study aimed to evaluate the neonate HPA axis function and maternal care under control and stress conditions in the WAR strain. Maternal behavior and neonate HPA axis were evaluated in Wistar and WAR strains under rest and after the presence of stressors. We observed that WAR pups present higher plasmatic corticosterone concentration as compared to Wistar pups. Although WAR dams do not show significant altered maternal behavior at rest, there is a higher latency to recover the litter in the pup retrieval test, while some did not recover all the litter. WAR dams presented similar behaviors to Wistar dams to a female intruder and maternal care with the pups in the maternal defense test. Taken together, these findings indicate that the WAR strain could show HPA axis disruption early in life and dams present altered maternal behavior under stressful events. Those alterations make the WAR strain an interesting model to evaluate vulnerability to epilepsy and its associated neuropsychiatric comorbidities.

Feed Restriction Induced Changes in Behavior, Corticosterone, and Microbial Programming in Slow- and Fast-Growing Chicken Breeds

This study aimed to explore the difference between two Chinese local broilers, one slow- and one fast-growing, in their response to a stress challenge. We conducted the study on slow- (Weining chicken) and fast-growing (Jinlinghua chicken) breeds, with 50 chickens from each breed either feed restricted to 70% for 30 days as a stress or given ad libitum to evaluate the effects on behavior, corticosterone, and microbial programming. Standing behavior was more frequent while exploration was less common in fast-growing breeds compared to slow-growing breeds. Food seeking and ingestion, exploration, and drinking increased, while resting decreased in the feed restricted treatments. There was no difference in corticosterone concentration between slow- and fast-growing chickens, but the level was affected by feeding treatments, and the interaction of breed and feed restriction. At the genus-level, the relative abundance of Bacteroides and Lactobacillus was higher, while Cloacibacillus and Megasphaera was lower in the slow-growing breed compared to the fast-growing breed. Feed restricted birds had a higher abundance of Mucispirillum, but lower abundance of Cloacibacillus, Clostridium XlVa and Clostridium IV. In conclusion, feed restriction to 70% for 30 days as a chronic stress stimulation caused more activity, elevated the stress response, and altered gut microbiota composition, but some changes were only evident in slow- or fast-growing chickens.

Effects of Sesame Oil Aroma on Mice after Exposure to Water Immersion Stress: Analysis of Behavior and Gene Expression in the Brain

(1) Background: Sesame has been popular as a healthy food since ancient times, and effects of the aroma component of roasted sesame are also expected. However, little research has been reported on its scent; (2) Methods: Jcl:ICR male mice were housed under water immersion stress for 24 h. Then, the scent of saline or sesame oil was inhaled to stress groups for 90 min. We investigated the effects of sesame oil aroma on the behavior and brains of mice; (3) Results: In an elevated plus maze test, the rate of entering to open arm and the staying time were decreased by the stress. These decrements were significantly enhanced by sesame oil aroma. Stress had a tendency to increase the serum corticosterone concentration, which was slightly decreased by the aroma. Expression of Kruppel-like factor-4 (Klf-4) and Dual-specificity phosphatase-1 (Dusp-1) in the striatum were increased by water immersion stress, and the level of Klf-4 and Dusp-1 in the striatum and hippocampus were significantly attenuated by sesame oil aroma (4) Conclusions: The present results strongly suggest that the odor component of sesame oil may have stress suppressing effects. Moreover, Klf-4 and Dusp-1 may be sensitive stress-responsive biomarkers.

Effect of cold and warm white light on selected endocrine and immune parameters of broiler embryos and hatchlings

Lighting conditions during incubation can influence embryonic development, post-hatching ontogeny and production efficiency. Previous studies revealed that different light colours differently affect pineal melatonin biosynthesis in embryos and postembryonic development of broiler chickens, but physiological mechanisms mediating these effects are not known. Cold and warm white light consists of different wavelengths and therefore the aim of the present study was to explore if these two lights can differently influence the development of circadian melatonin biosynthesis, production of thyroid hormones and corticosterone, concentration of metabolites (glucose, cholesterol and triacylglycerols) as well as expression of two important immune genes, presenilin 1 and avian beta-defensin 1 (AvBD-1). We evaluated these traits in embryos before hatching (456, 460, 465, 468 and 472 h of incubation) and in hatchlings. The rhythmic profile of pineal melatonin with higher concentrations during the dark time was determined in both treatment groups. Melatonin levels increased considerably in hatchlings in comparison with embryos, but we found no difference in rhythm characteristics between groups. We did not identify any daily rhythms in plasma corticosterone and thyroid hormone levels in either studied age and no differences were found between light treatments in concentrations of thyroid hormones, corticosterone, metabolites and expression of presenilin and AvBD-1. The expected developmental increase of thyroid hormones was proved. Gene expression of presenilin increased in the duodenum of hatchlings in comparison with embryos, but the expression did not change in the bursa of Fabricius. On the other hand, expression of AvBD-1 decreased in hatchlings compared to embryos in both tissues. Based on these results, we can conclude that the colour temperature of white light did not influence endocrine and immune parameters determined in this study and probably monochromatic rather than polychromatic light should be used to influence embryonic development and postembryonic ontogeny of broiler chickens.