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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Schizophrenia is a neurodevelopmental disorder with dendrite and dendritic spine dysfunction. Dysbindin-1, a protein decreased in the brains of schizophrenia patients, is involved in the development of dendrites and spines. However, it is still unclear how the role of dysbindin-1 in neuronal development is regulated. ⋯ S10 phosphorylation of dysbindin-1A was increased during postnatal neuronal and synapse development stage, and was enriched in postsynaptic densities (PSDs). Furthermore, overexpressing wild type or S10 phospho-mimic mutant (S10D), but not S10 phospho-dead mutant (S10A) of dysbindin-1A rescued the dendrite and spine deficits in dysbindin-1A knockdown neurons. These results indicate S10 phosphorylation of dysbindin-1A by Akt1 is essential for neuronal development, providing a potential regulation mechanism for dysbindin-1A in neuronal development.
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The impacts of early-life adversity (ELA) on cognitive functions including striatal-dependent habit memory and hippocampal-dependent spatial memory were investigated in male mice. The ELA mouse model was generated via an altered cage environment with limited nesting and bedding materials during postnatal days 2-9 (P2-9). The altered cage environment affected the nesting behaviors of dams, creating a stressful condition for their offspring. ⋯ The spine data supported the selective effects of ELA on PSD-95 synapses. Specifically, both thin and mushroom-type spines were increased in DLS, while loss of thin spines was apparent in CA1 radiatum in ELA mice versus controls. The correlation between PSD-95 synapses and memory performances was further analyzed, and the data suggested that increased small (<0.20 μm3) and large (>0.40 μm3) synapses in DLS might drive ELA mice to make decisions largely relying on habit memory, while loss of small synapses in hippocampal CA1 damage the spatial memory of ELA mice.
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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.
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N-methyl-d-aspartate receptor-mediated ( spikes can be causally linked to the induction of synaptic long-term potentiation (LTP) in hippocampal and cortical pyramidal cells. However, it is unclear if they regulate plasticity at a local or global scale in the dendritic tree. ⋯ We show that local hyperpolarization of a single dendritic segment prevents NMDA spikes, their associated calcium transients, as well as LTP in a branch-specific manner. This result provides direct, causal evidence that the single dendritic branch can operate as a functional unit in regulating CA3 pyramidal cell plasticity.