Pubertal probiotics mitigate lipopolysaccharide-induced programming of the hypothalamic-pituitary-adrenal axis in male mice only.

Puberty is a period of rapid cortical and neuronal development. Stress exposure during puberty programs the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to future stressors. However, programming can result in an enduring maladaptation of the HPA axis activity and can be associated with long-term anxiety- and depression-like behaviours. Probiotic treatment mitigates the effect of stress on mental health, suggesting that the gut microbiome may mediate the programming of the HPA axis. However, the mechanism underlying this effect remains elusive. Thus, we investigated the effect of probiotic exposure on lipopolysaccharide (LPS)-induced programming of the HPA axis and glucocorticoid receptor (GR) expression in the paraventricular (PVN), basolateral amygdala (BLA), piriform cortex (PIR), and medial prefrontal cortex (mPFC). Male and female mice were exposed to either probiotics or control skim milk and were treated with either saline or LPS during puberty. Prior to euthanasia in adulthood, mice were restrained for 30 min. The results showed that pubertal LPS treatment permanently decreased GR expression in the PVN in milk fed control males. However, pubertal probiotic treatment blocked the LPS-induced decrease in GR expression in males. Given that this effect is limited to males, further research is required to better understand sex differences in the interactions between the gut microbiome and the programming of the HPA axis during puberty. Nevertheless, our findings suggest that the gut microbiome influences the neurophysiology of the HPA axis and mediates its programming in pubertal males. The prevention of GR reduction in the male PVN and PIR using probiotics illustrates the complexity of the gut-brain communication and compels continued investigation.

Estradiol potentiates inhibitory synaptic transmission in the oval bed nucleus of the striaterminalis of male and female rats.

17ß-Estradiol (E2) is a potent neuromodulator capable of producing changes in inhibitory synaptic transmission by either changing pre-synaptic GABA release or post-synaptic GABAA receptor function. Physiologically, E2 is important for energy homeostasis, influencing food consumption, body weight, adipose tissue metabolism and energy expenditure. E2 may influence energy homeostasis through estrogen receptor-rich regions such as the oval bed nucleus of the stria-terminalis (ovBNST). However, the neurophysiological effects of estradiol within the ovBNST remain largely unknown. Understanding how E2 affects inhibitory transmission may elucidate the ovBNST's contribution to energy homeostasis. Here, using brain slice electrophysiology, we saw that E2 produced a long-term potentiation (LTP) of GABAA synaptic transmission (LTPGABA) in the ovBNST in male rats. E2 acted on estrogen receptors α and G-protein coupled estrogen receptors (GPER), involved protein kinase activation and required an intact endocannabinoid system. The effects of E2 in males were sensitive to 24 h of food deprivation. In females, E2 was 100-fold more potent at producing LTPGABA ovBNST compared to male rats and involved all three known subtypes of estrogen receptors (ERα, ERß, and GPER). These results demonstrate that E2 is a potent neuromodulator of inhibitory synaptic transmission within the ovBNST of both sexes to potentially regulate energy homeostasis.

Pubertal immune stress transiently alters spatial memory processes in adulthood.

Pubertal immune challenge can permanently alter hippocampus-dependent memory processes in a sex-specific manner. Although gonadal hormones can influence various cognitive processes, their role in regulating the cognitive sequelae to pubertal immune challenge has not been thoroughly assessed. We examined whether a pubertal immune challenge could affect hippocampus-dependent memory functions in adulthood and whether these effects are regulated by gonadal steroid hormones. We hypothesized that exposure to an immune challenge during puberty would induce sex-specific deficits in the behavioral and cellular correlates of hippocampus-dependent memory during adulthood. At six weeks of age, during the stress-vulnerable pubertal period, male and female CD-1 mice were injected with either saline or the bacterial endotoxin lipopolysaccharide (LPS). Three weeks later, mice underwent either gonadectomy or sham-surgery. At ten weeks of age (i.e., in adulthood), mice began behavioral testing in an open field, Barnes maze, and Morris water maze. Brain tissue was collected at 17 weeks of age and stained for doublecortin and Ki67 to examine migrating neuronal progenitor cells and cellular proliferation in the neurogenic subgranular zone (SGZ) and the cornus ammonis (CA)1 and CA3 regions of the hippocampus. Pubertal LPS treatment impaired learning during adulthood in both sexes and increased cellular proliferation in the CA1 region in castrated males only. Although adult sex hormones did not reliably modulate these changes, gonadectomy impaired learning during the Morris water maze in both sexes. Learning deficits were more prominent during the Barnes maze, which suggests a stress-dependent expression of LPS-induced cognitive deficits. Neurogenesis in the SGZ and cellular proliferation in the CA3 were not affected by pubertal LPS treatment or gonadectomy. These novel findings emphasize the sensitivity of developing cognitive processes during puberty to immune challenges and suggest a possible mechanism for learning-based difficulties in adulthood.

The manic phase of Bipolar disorder significantly impairs theory of mind decoding.

Bipolar disorder is associated with significant deficits in the decoding of others' mental states in comparison to healthy participants. However, differences in theory of mind decoding ability among patients in manic, depressed, and euthymic phases of bipolar disorder is currently unknown. Fifty-nine patients with bipolar I or II disorder (13 manic, 25 depressed, 20 euthymic) completed the "Reading the Mind in the Eyes" Task (Eyes task) and the Animals Task developed to control for non-mentalistic response demands of the Eyes Task. Patients also completed self-report and clinician-rated measures of depression, mania, and anxiety symptoms. Patients in the manic phase were significantly less accurate than those in the depressed and euthymic phases at decoding mental states in the Eyes task, and this effect was strongest for eyes of a positive or neutral valence. Further Eyes task performance was negatively correlated with the symptoms of language/thought disorder, pressured speech, and disorganized thoughts and appearance. These effects held when controlling for accuracy on the Animals task, response times, and relevant demographic and clinical covariates. Results suggest that the state of mania, and particularly psychotic symptoms that may overlap with the schizophrenia spectrum, are most strongly related to social cognitive deficits in bipolar disorder.

A response strategy predicts acquisition of schedule-induced polydipsia in rats.

Schedule-induced polydipsia (SIP) is excessive, non-regulatory drinking. We aimed to identify phenotypic learning traits representative of neural circuitry that underlies SIP and hypothesized that rats that are response-learners will be more susceptible in developing compulsive water drinking. Using the Y-maze, the rats were characterized as either place- or response-learners. They were exposed to the SIP protocol for a period of 21days. Subsequent histological staining for FosB/ΔFosB examined neuronal activation associated with SIP in several brain regions. The rats with a preference for a response-learning strategy were more likely to develop SIP than the rats using a place-learning strategy. Furthermore amphetamine sensitization, observed to increase SIP, also shifted learning strategy to a response-learning strategy. No differences were observed in FosB/ΔFosB expression between SIP and non-SIP rats in the dorsolateral striatum (DLS) and CA1 region of the hippocampus. However, SIP rats had greater FosB/ΔFosB expression in prefrontal cortex regions. The rats that develop SIP have a preference for response-learning strategies and increased neuronal activation in frontal cortical regions associated with habit formation and compulsion.

Sensitization of sexual behavior in ovariectomized rats by chronic estradiol treatment.

The ovariectomized (OVX) rat treated with estradiol benzoate (EB) is used to elucidate neuroendocrine mechanisms of sexual behavior. Chronic behavioral and pharmacological manipulations can be confounded by rising baselines, since females are behaviorally more sensitive to repeated EB injections. The literature lacks a systematic examination of chronic effects of EB administered alone to the sexually experienced OVX rat. Long-Evans rats were repeatedly treated (8 tests) with s.c. injections of 2, 5, or 10 µg EB at different time intervals (4 or 8 days). Female sexual behaviors as well as receipt of mounts, intromissions and ejaculations from the male were observed in the unilevel 4-hole pacing chamber. The effects of adrenalectomy (ADX) and strain (Long-Evans vs. Wistar) were also assessed. Long-Evans OVX rats treated with 5 µg EB every 8 days showed persistently low levels of sexual behavior. Sensitization was most robust following 10 µg EB at 4-day intervals. Very few sexual behaviors were ever induced by 2 µg EB. ADX did not affect the development of behavioral sensitization by 10µg EB. Therefore, to achieve a low steady state of sexual behaviors in sexually experienced Long-Evans OVX rats 5µg of EB administered every 8days is optimal, whereas a persistently high level of sexual behaviors is induced with 10 µg EB administered every 4 days. OVX Wistar rats are behaviorally more sensitive to EB. Behavioral sensitization to EB may serve as a mechanism to optimize reproductive success.