Intergenerational changes in hippocampal transcription in an animal model of maternal depression

Chronic stress during early life, such as exposure to social conflict or deficits in parental care, can have persistent adverse behavioural effects. Offspring in a rodent model of maternal depression and early life stress have increased susceptibility to maternal depression themselves, suggesting a pathway by which maternal stress could be intergenerationally inherited. The overall aim of this study was to explore the genetic regulatory pathways underlying how maternal social stress and reduced care mediates stress‐related behavioural changes in offspring across generations. This study investigated a social stress‐based rat model of postpartum depression and the intergenerational inheritance of depressed maternal care where F0 (dams exposed to male intruder stress during lactation) and F1 offspring are directly exposed to social stress. RNASeq was used to investigate genomewide transcriptome changes in the hippocampus of F1 and F2 generations. Transcriptome analyses revealed differential expression of 69 genes in the F1 generation and 14 in the F2 between controls vs. social stress differences. Many of these genes were receptors and calciumbinding proteins in the F1 and involved in cellular oxidant detoxification in F2. The present data identify and characterize changes in the neural expression of key genes involved in the regulation of depression maintained between the generations, suggesting a potential neural pathway for the intergenerational transmission of depressed maternal care and maternal anxiety in the CSS model. Further work is needed to understand to what extent these results are due to molecular germline inheritance and/or the social propagation of deficits in maternal care

Sex Differences in Cognitive Flexibility and Resting Brain Networks in Middle-Aged Marmosets

Sex differences in human cognitive performance are well characterized. However, the neural correlates of these differences remain elusive. This issue may be clarified using nonhuman primates, for which sociocultural influences are minimized. We used the marmoset (Callithrix jacchus) to investigate sex differences in two aspects of executive function: reversal learning and intradimensional/extradimensional (ID/ED) set shifting. Stress reactivity and motor function were also assessed. In agreement with human literature, females needed more trials than males to acquire the reversals. No sex differences in ED set shifting or motivational measures were observed. The findings suggest enhanced habit formation in females, perhaps due to striatal estrogenic effects. Both sexes showed increased urinary cortisol during social separation stressor, but females showed an earlier increase in cortisol and a greater increase in agitated locomotion, possibly indicating enhanced stress reactivity. Independent of sex, basal cortisol predicted cognitive performance. No sex differences were found in motor performance. Associations between brain networks and reversal learning performance were investigated using resting state fMRI. Resting state functional connectivity (rsFC) analyses revealed sex differences in cognitive networks, with differences in overall neural network metrics and specific regions, including the prefrontal cortex, caudate, putamen, and nucleus accumbens. Correlations between cognitive flexibility and neural connectivity indicate that sex differences in cognitive flexibility are related to sex-dependent patterns of resting brain networks. Overall, our findings reveal sex differences in reversal learning, brain networks, and their relationship in the marmoset, positioning this species as an excellent model to investigate the biological basis of cognitive sex differences

Keeping weight off: Mindfulness-Based Stress Reduction alters amygdala functional connectivity during weight loss maintenance in a randomized control trial

Obesity is associated with significant comorbidities and financial costs. While behavioral interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. The objective was to improve understanding of the neural and psychological mechanisms modified by mindfulness that may predict clinical outcomes. Individuals who intentionally recently lost weight were randomized to Mindfulness-Based Stress Reduction (MBSR) or a control healthy living course. Anthropometric and psychological factors were measured at baseline, 8 weeks and 6 months. Functional connectivity (FC) analysis was performed at baseline and 8 weeks to examine FC changes between regions of interest selected a priori, and independent components identified by independent component analysis. The association of pre-post FC changes with 6-month weight and psychometric outcomes was then analyzed. Significant group x time interaction was found for FC between the amygdala and ventromedial prefrontal cortex, such that FC increased in the MBSR group and decreased in controls. Non-significant changes in weight were observed at 6 months, where the mindfulness group maintained their weight while the controls showed a weight increase of 3.4% in BMI. Change in FC at 8-weeks between ventromedial prefrontal cortex and several ROIs was associated with change in depression symptoms but not weight at 6 months. This pilot study provides preliminary evidence of neural mechanisms that may be involved in MBSR\u27s impact on weight loss maintenance that may be useful for designing future clinical trials and mechanistic studies

GABAergic inhibition is weakened or converted into excitation in the oxytocin and vasopressin neurons of the lactating rat

BACKGROUND: Increased secretion of oxytocin and arginine vasopressin (AVP) from hypothalamic magnocellular neurosecretory cells (MNCs) is a key physiological response to lactation. In the current study, we sought to test the hypothesis that the GABA(A) receptor-mediated inhibition of MNCs is altered in lactating rats. RESULTS: Gramicidin-perforated recordings in the rat supraoptic nucleus (SON) slices revealed that the reversal potential of GABA(A) receptor-mediated response (E(GABA)) of MNCs was significantly depolarized in the lactating rats as compared to virgin animals. The depolarizing E(GABA) shift was much larger in rats in third, than first, lactation such that GABA exerted an excitatory, instead of inhibitory, effect in most of the MNCs of these multiparous rats. Immunohistochemical analyses confirmed that GABAergic excitation was found in both AVP and oxytocin neurons within the MNC population. Pharmacological experiments indicated that the up-regulation of the Cl(−) importer Na(+)-K(+)-2Cl(−) cotransporter isotype 1 and the down-regulation of the Cl(−) extruder K(+)-Cl(−) cotransporter isotype 2 were responsible for the depolarizing shift of E(GABA) and the resultant emergence of GABAergic excitation in the MNCs of the multiparous rats. CONCLUSION: We conclude that, in primiparous rats, the GABAergic inhibition of MNCs is weakened during the period of lactation while, in multiparous females, GABA becomes excitatory in a majority of the cells. This reproductive experience-dependent alteration of GABAergic transmission may help to increase the secretion of oxytocin and AVP during the period of lactation