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Altered Cellular Distribution of Phospho-Tau Proteins Coincides with Impaired Retrograde Axonal Transport in Neurons of Aged Rats

机译:磷酸盐蛋白的改变细胞分布与老鼠神经元中的逆行轴突运输受损

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We hypothesize that the age-related degeneration of cytoskeleton in basal forebrain cholinergic neurons renders the NGF-TrkA signaling system non-functional and thereby impairs trophic support. Comparing young (4 months) and aged (28 months) rat brain, we examined immunohistochemically the compartmentalization of phosphorylated Tau protein using antibodies phospho-Tau404 and phospho-Tau231 of the GSK3β kinase, known to phosphorylate Tau, the neurotrophin NGF, and its receptor P-TrkA. Retrograde labeling of basal forebrain cholinergic cells after injection of fluorogold into multiple sites in cortex and hippocampus revealed a significantly lower number of fluorogold-positive cells in aged brain. Despite a lower density of P-TrkA immunoreactivity in cortex and hippocampus of aged rats, there was no difference in NGF expression. In young animals phospho-Tau404, phospho-Tau231, and GSK3 immunoreactivity was observed mainly in neuronal fibers with lower staining in somata both in cortex and hippocampus. By contrast, Tau and GSK3 labeling were confined to the cell bodies in aged rats. This is confirmation that aging leads to a redistribution of cytoskeletal proteins. Since a somatic localization of phospho-Tau is indicative of cytoskeletal breakdown, we suggest that failure of axonal trafficking may be responsible for the lack of trophic support in aged cholinergic neurons of the basal forebrain.
机译:我们假设基础前脑中胆碱机神经元中的细胞骨架的年龄相关退化使NGF-TRKA信号传导系统非功能性,从而损害营养载体。比较年轻(4个月)和年龄(28个月)大鼠大脑,我们使用GSK3β激酶的抗体磷酸盐-Tau404和磷酸化性磷酸磷酸磷酸盐磷酸磷酸化学磷酸化化学的分区化,已知为磷酸化,神经营养不良的NGF及其受体p-trka。将氟代胶胆碱能细胞注射到皮质和海马中的多个位点后,逆行标记基础前脑胆碱能细胞显示出在老年脑中的含氟含量阳性细胞数量显着较低。尽管在老鼠的皮质和海马中p-trka免疫反应性较低,但NGF表达没有差异。在幼小动物中,磷酸盐Tau404,磷酸盐-Tau231和GSK3免疫反应性主要观察到神经元纤维,在皮质和海马中的躯体较低。相比之下,Tau和GSK3标记被限制在老年大鼠中的细胞体上。这是确认老化导致细胞骨骼蛋白的重新分布。由于磷脂的体细胞定位表示是细胞骨架崩溃,因此我们建议轴突贩运的失败可能是缺乏基础前脑的胆碱能神经元中的营养载体。

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