Neuroscience
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Trauma and tumor compressing the brain distort underlying cortical neurons. Compressed cortical neurons remodel their dendrites instantly. The effects on axons however remain unclear. ⋯ However, KLC and KHC expressions in the cell bodies of the layer II/III pyramidal neurons partially recovered. Our results show cerebral compression compromised cortical axonal outputs and reduced transcallosal projection. Some of these changes did not recover in long-term decompression.
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Although deep-brain stimulation (DBS) of the lateral habenula (LHb) has been successfully applied to treatment-resistant depression for years, the mechanism is still unclear. Previous researches have demonstrated that LHb-DBS elevates brain monoamine neurotransmitters. However, these changes do not account for the treatment efficacy on treatment-resistant depression, or the rapid behavioral effects in rats; the evidence suggests that altered synaptic potentiation may contribute to the treatment effects. ⋯ These effects were blocked by the L-type voltage-dependent calcium channel (L-VDCC) antagonist, nifedipine. Furthermore, in vitro LHb-DBS increased both the frequency and width of spontaneous spikes generated by CA1 pyramidal neurons, which contribute to Ca2+ influx through L-VDCC. Our findings suggest that L-VDCC-mediated synaptic potentiation underlies the antidepressant effects of LHb-DBS, and suggest that astrocytic regulation of Ca2+ influx and associated synaptic changes maybe novel targets for developing antidepressant treatments.
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Neuregulin-1β (NRG-1β) has great potential to be developed into therapeutics for neuroprotection. The aim of the current study was to analyze the effects and possible signaling pathway of NRG-1β on brain tissues in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). ⋯ NRG-1β exerts a neuroprotective effect through the JNK signaling pathway in MCAO/R rats.
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The dysregulation of posttranslational modifications of the microtubule-associated protein (MAP) tau plays a key role in Alzheimer's disease (AD) and related disorders. Thus, we have previously shown that beta amyloid (Aβ)-induced neurotoxicity was mediated, at least in part, by tau cleavage into the tau45-230 fragment. However, the mechanisms underlying the toxicity of tau45-230 remain unknown. ⋯ Our results indicated that tau45-230 significantly reduced the number of organelles transported along hippocampal axons. This altered axonal transport did not correlate with changes in the total number of organelles present in these cells or in motor protein levels. Together these results suggested that tau45-230 could exert its toxic effects by partially blocking axonal transport along microtubules thus contributing to the early pathology of AD.
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Sestrin 2 (SESN2) is a stress-inducible protein that protects tissues from oxidative stress and delays the aging process. However, its role in maintaining the functional and structural integrity of the cochlea is largely unknown. Here, we report the expression of SESN2 protein in the sensory epithelium, particularly in hair cells. ⋯ Hair cell death occurred by caspase-8 mediated apoptosis. Compared to C57BL/6J control mice, Sesn2 KO mice displayed enhanced expression of proinflammatory genes and activation of basilar membrane macrophages, suggesting that loss of SESN2 function provokes the immune response. Together, these results suggest that Sesn2 plays an important role in cochlear homeostasis and immune responses to stress.