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Tau protein is involved in morphological plasticity in hippocampal neurons in response to BDNF

机译:Tau蛋白参与对BDNF响应的海马神经元的形态可塑性

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摘要

Tau protein, a microtubule-associated protein involved in a number of neurological disorders such as Alzheimer's disease (AD), may undergo modifications under both physiological and pathological conditions. However, the signaling pathways that couple tau protein to neuronal physiology such as synaptic plasticity have not yet been elucidated. Here we report that tau protein is involved in morphological plasticity in response to brain derived neurotrophic factor (BDNF). Stimulation of the cultured rat hippocampal neurons with BDNF resulted in increased tau protein expression, as detected by Western blotting. Furthermore, tau protein accumulated in the distal region of the neurite when treated with taxol or taxol plus BDNF. The increased tau protein also protected neurons against nocodazole-induced dendrite loss. Moreover, BDNF promoted spine growth as well as tau protein over-expression. Knockdown of tau protein using specific short-hairpin RNA (shRNA) significantly decreased the spine density. And BDNF could not increase the spine density of tau-knockdown neurons. These results highlight a possible role for tau protein in the dynamic rearrangement of cytoskeletal fibers vital for BDNF-induced synaptic plasticity.
机译:Tau蛋白是一种涉及许多神经系统疾病(例如阿尔茨海默氏病(AD))的微管相关蛋白,在生理和病理条件下都可能发生修饰。但是,尚未阐明将tau蛋白偶联至神经元生理学(例如突触可塑性)的信号传导途径。在这里我们报告说,tau蛋白参与了对脑源性神经营养因子(BDNF)的反应的形态可塑性。如通过蛋白质印迹所检测,用BDNF刺激培养的大鼠海马神经元导致tau蛋白表达增加。此外,当用紫杉醇或紫杉醇加BDNF处理时,tau蛋白积聚在神经突的远端区域。增加的tau蛋白还可以保护神经元免受诺考达唑诱导的树突丢失。此外,BDNF促进了脊柱生长以及tau蛋白的过度表达。使用特异性短发夹RNA(shRNA)抑制tau蛋白可显着降低脊柱密度。 BDNF不能增加tau基因敲除神经元的脊柱密度。这些结果突出了tau蛋白在对BDNF诱导的突触可塑性至关重要的细胞骨架纤维的动态重排中的可能作用。

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