Neuroscience
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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.
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Post-weaning is a critical period for brain maturation in the rat and is comparable to childhood and adolescences in humans. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) are two brain regions that continue to mature during post-weaning and establish a critical circuit regulating the acquisition and extinction of conditioned fear. We previously demonstrated that exposure to stress leads to significant differences between adults and PWs in the kinetics of extinction behavior as well as differential effects on long-term potentiation. ⋯ Further, freezing levels during extinction positively correlated with the magnitude of LTP only in adult animals. These results suggest that the changes occurring at the synaptic level following fear extinction are dissimilar in adult and PW animals. Our results further strengthen the assertion that PW and adult fear extinction learning may rely on different mechanisms.
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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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Orexin and melanin-concentrating hormone (MCH) neurons constitute the energy balance circuitry that coordinates the fasting response. Orexin neurons mediate food foraging at the expense of energy storage, while MCH neurons promote energy storage by reducing energy expenditure and increasing food intake. It is unknown if these cell groups undergo plastic changes as hunger and metabolic changes escalate over time during fasting. ⋯ Our results indicate that MCH neurons are preferentially activated during the early phase of fasting (12 h), which would protect against weight loss. With a longer fast, orexin neurons become activated, which would promote arousal and exploratory activity required for foraging behaviors. This alternating activation of these cell groups may reflect a dynamic balance of energy conservation and foraging behaviors to optimize energy balance during ongoing fasting.
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Peripheral nerve injury (PNI) is a common disease that causes the partial loss of sensory, exercise, and autonomic nervous function. In clinical practice, accurate end-to-end neurorrhaphy of the epineurium without tension is the ideal treatment when there is no nerve defect. We have confirmed that peripheral blood mononuclear cells (PBMCs) can effectively improve nerve regeneration and motor function recovery after PNI. ⋯ We then used TMT labeling quantitative proteomics to explore the underlying mechanism by which PBMCs ameliorated sciatic nerve injury. Results showed that PBMCs regulated 40 differential proteins and the regulated proteins were primarily involved in the complement and coagulation cascade pathways, the notch signaling pathway, the renin angiotensin system, DNA replication, histidine metabolism, β-alanine metabolism, and other types of O-glycan biosynthesis. Immunohistochemical results supported our findings on the changes in expression of Kininogen 1 and Psen1, the relationships between PNI and the notch pathway and the complement and coagulation level pathways.