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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Under normal conditions, dopamine (DA) clearance after release largely depends on uptake by the DA transporter (DAT). DAT expression/activity is reduced in some neuropsychiatric and neurological disorders. Our aim was to characterize the behavioral, neurochemical and electrophysiological effects of eliminating DAT in a novel knockout rat model we generated using CRISPR/Cas9. ⋯ However, D2 receptor-mediated inhibition of firing (by quinpirole or L-DOPA) was blunted in DAT-KO rats, while GABAB-mediated inhibition was preserved. We have also provided new data for the DAT-KO rat regarding the effects of slowing DA diffusion with dextran and blocking organic cation transporter 3 with corticosterone. Together, our results validate our DAT-KO rat and provide new insights into the mechanisms of chronic dysregulation of the DA system by addressing several unresolved issues in previous studies with other DAT-KO models.
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Although various studies have reported a high prevalence of depression among Parkinson's disease (PD) patients, the pathophysiological mechanism of depression in PD (DPD) is still unclear. The core region of the reward network, the ventral striatum (VS), is critical in the occurrence and development of DPD. This study aimed to explore the altered functional connectivity (FC) of VS subregions in DPD. ⋯ The hyperconnectivity between vCa_L and the MOG. L might be viewed as a compensatory mechanism for depression in the early stage of PD. This study provides new insight into the neural mechanism of depression in the early stage of PD and contributes to explore the potential neuroimaging markers for DPD.
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Growing evidence has demonstrated that treadmill exercise is beneficial to increase β-amyloid (Aβ) clearance and protect against Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. Recently, microglia dysfunction leading to Aβ clearance impairment is proved an important mechanism for later Aβ deposition and AD pathogenesis. ⋯ Moreover, treadmill exercise partly restored microglial Aβ degradation and clearance in the hippocampus, which was impaired in APP/PS1 mice. However, the impaired microglial Aβ phagocytosis in APP/PS1 mice was not altered after 3 months of treadmill exercise intervention. These findings demonstrate that 3 months of treadmill exercise alleviates hippocampal Aβ deposition and restores spatial learning and memory in APP/PS1 mice, partly by promoting microglial Aβ degradation and clearance.
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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.