Dewar D, Dawson D
Wellcome Surgical Institute, University of Glasgow, UK.
Brain Res. 1995 Jun 26;684(1):70-8. doi: 10.1016/0006-8993(95)00417-o.
Breakdown of the cytoskeleton may be involved in the evolution of ischaemic brain damage and alterations in microtubule-associated proteins may play an important role in this process. In the present study, tau, a microtubule-associated protein predominantly located in axons, was examined after 2 or 6 h of focal cerebral ischaemia in the rat. Immunohistochemistry revealed increased Tau1 staining in the neuropil, some perikarya and in glial cells throughout the dorsolateral caudate nucleus and ventrolateral neocortex in the ipsilateral hemisphere at both 2 and 6 h after occlusion of the middle cerebral artery. Contrastingly, immunostaining of another tau antibody, TP70, was unchanged in the neuropil, but was increased specifically in glial cells in these regions. Immunoblotting revealed the presence of additional tau bands in tissue extracts of the caudate nucleus and ventrolateral neocortex ipsilateral to the occluded middle cerebral artery as detected by both tau antibodies after either 2 or 6 h. The results suggest that tau is dephosphorylated and/or degraded in axons and some neuronal perikarya in response to focal cerebral ischaemia. In contrast to the response in neurons, increased immunoreactivity of both tau antibodies in glial cells indicates a differential response of neuronal and glial tau to focal cerebral ischaemia.
细胞骨架的破坏可能参与了缺血性脑损伤的进展，微管相关蛋白的改变可能在此过程中起重要作用。在本研究中，我们检测了大鼠局灶性脑缺血2小时或6小时后，一种主要位于轴突的微管相关蛋白——tau蛋白。免疫组织化学显示，大脑中动脉闭塞后2小时和6小时，同侧半球背外侧尾状核和腹外侧新皮质的神经毡、一些核周体和神经胶质细胞中，Tau1染色增加。相比之下，另一种tau抗体TP70在神经毡中的免疫染色没有变化，但在这些区域的神经胶质细胞中特异性增加。免疫印迹显示，在闭塞大脑中动脉同侧的尾状核和腹外侧新皮质组织提取物中，两种tau抗体在2小时或6小时后均检测到额外的tau条带。结果表明，tau蛋白在轴突和一些神经元核周体中因局灶性脑缺血而发生去磷酸化和/或降解。与神经元的反应不同，两种tau抗体在神经胶质细胞中的免疫反应性增加表明神经元tau蛋白和神经胶质tau蛋白对局灶性脑缺血的反应不同。
