Neuroscience
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Increasing evidence has shown that early life events exert long-lasting effects on brain function and mental diseases. Exercise has been proven to have many positive effects on behaviors, such as reducing anxiety- and depression-like behaviors and alleviating cognitive impairment. However, the long-lasting and even short-term effects of regular swimming exercise on social dominance remain unclear. ⋯ There was no difference between the swimming and sedentary groups in anxiety- and depression-like behaviors. Metabolomics analysis showed that there were alterations in particular metabolites and signaling pathways after one month of swimming exercise, including sphingolipid metabolism, neuroactive ligand-receptor interaction and caffeine metabolism. In conclusion, our results provide the first evidence that postweaning swimming exercise has long-lasting and sex-dependent effects on social dominance, which may be caused by metabolic adaptation.
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Modern westernized diet is a major risk factor associated with the current obesity epidemic. To study the effects of dietary choices of Western societies, the cafeteria diet has been validated as a preclinical model of obesity. We aimed to investigate the behavioral and metabolic alterations induced by a cafeteria diet on gene expression and neurotransmitter contents involved in neural plasticity and reward processing. ⋯ The cafeteria diet increased BDNF expression in the dorsal striatum (DS), and norepinephrine, 5-HT, TrkB, CREB, and Dnmt3A levels in the hippocampus. Additionally, multiple regression analysis showed that accumbal DOPAC and BDNF mRNA levels were robustly predicted by hyperphagia, fat mass accumulation, and body weight gain only in the cafeteria group. Overall, cafeteria diet-induced hyperphagia could lead to alterations in hedonic and motivational control of food intake through changes in dopamine metabolism and BDNF signaling in the nucleus accumbens and the DS.
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Our previous studies revealed that miR-34a suppresses autophagy in the ageing cochlea, which correlates with cochlear hair cell loss and age-related hearing loss (AHL). However, the mechanisms underlying miR-34a regulation of autophagy in the cochlea remain unclear. Here, we show that nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy, was regulated by miR-34a in HEI-OC1 cells. ⋯ Long-term supplementation with rapamycin attenuated outer hair cells (OHCs) and inner hair cell synaptic ribbons, and delayed AHL in C57BL/6 mice. Most importantly, rapamycin partially restored TFEB's nuclear localization and autophagic flux in OHCs of the ageing cochlea. These findings open new avenues for protection against AHL through miR-34a/ATG9a/TFEB modulation of autophagy.
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Stress-related mood disorders like anxiety and depression are more prevalent in women than men and are often associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Androgen actions through androgen receptors (ARs) decrease HPA axis responses and stress-associated behaviors. Corticotropin releasing factor (CRF) and its binding to CRF receptor 1 (CRFR1) is also critical for regulation of the HPA axis, anxiety, and depression. ⋯ Following restraint stress GDX-blank mice showed fewer c-Fos/CRFR1 co-localized neurons in the MePD compared to gonad intact and GDX-DHT groups indicating decreased stress-induced activation of CRFR1 neurons following GDX. Higher plasma corticosterone (CORT) was found in GDX males compared to GDX-DHT and sham males following restraint stress, with a negative correlation between PVN CRFR1+ neurons and corticosterone levels 30- and 90-min following restraint. Together these findings show androgens can directly alter CRFR1 levels in the brain which may have implications for sex differences in regulation of the HPA axis and stress-related behaviors.