Compartmental protein expression of Tau, GSK-3β and TrkA in cholinergic neurons of aged rats
Compartmental protein expression of Tau, GSK-3β and TrkA in cholinergic neurons of aged rats
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DOI：
10.1007/s00702-006-0488-4
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发表时间：
2006-11-01
影响因子：
3.3
通讯作者：
Riedel, G.
中科院分区：
文献类型：
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作者：
Niewiadomska, G.;Baksalerska-Pazera, M.;Riedel, G.
在衰老过程中，基底前脑胆碱能神经元(BFCNs)退化，我们假设这是细胞骨架退化的结果。因此，神经生长因子(NGF)及其活化受体磷酸TrkA(P-TrkA)复合体的逆行转运受损。利用免疫细胞化学，我们比较了年轻和老年大鼠脑内NGF和P-TrkA的亚细胞定位与磷酸化依赖的tau蛋白亚型的区域化的关系。尽管老年大鼠大脑皮质和海马区P-TrkA免疫反应性降低，但NGF免疫反应性在这些区域没有改变，但在老年基底前脑中显著降低。在幼年动物中，tau异构体和糖原合成酶激酶-3β(GSK-3β)的表达仅限于皮质、海马和基底前脑的神经性结构。相反，tau和GSK-3β标记仅限于老年大鼠的细胞体。由于磷酸化tau的体细胞定位是细胞骨架崩溃的标志，我们认为这是老化的BFCNs营养支持崩溃的机制。
During aging basal forebrain cholinergic neurons (BFCNs) degenerate, and we hypothesize this to be the result of a degeneration of the cytoskeleton. As a corollary, retrograde transport of the complex of nerve growth factor (NGF) and its activated receptor phospho-TrkA (P-TrkA) is impaired. Using immunocytochemistry, we here compare young and aged rat brains in their subcellular localization of NGF and P-TrkA in relation to the compartmentalization of phosphorylation-dependent tau protein isoforms. Despite lower P-TrkA immunoreactivity in cortex and hippocampus of aged rats, NGF immunoreactivity was not altered in these areas, but was significantly lower in aged basal forebrain. In young animals, expression of tau isoforms and glycogen synthase kinase-3 beta (GSK-3 beta) was restricted to neuritic structures in cortex, hippocampus, and basal forebrain. In contrast, tau and GSK-3 beta labeling was confined to cell bodies in aged rats. Since a somatic localization of phospho-tau is indicative of cytoskeletal breakdown, we suggest this to be the mechanism the breakdown of trophic support in aging BFCNs.