Yamada K, Goto S, Ushio Y
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Neuroscience. 1994 Oct;62(3):793-801. doi: 10.1016/0306-4522(94)90477-4.
The substantia nigra is innervated by massive inhibitory GABAergic projections from the striatum and globus pallidus, deafferentation of which is supposed to lead to anterograde trans-synaptic degeneration of the nigral neurons. An immunohistochemical method was used to examine the induction of 72,000 mol. wt heat shock protein in the substantia nigra following cerebral hemitransection or transient middle cerebral artery occlusion. At three and four days post-transection, strong immunoreactivity for 72,000 mol. wt heat shock protein was found in the ipsilateral substantia nigra pars reticulata. Light microscopic observation revealed a number of pars reticulata neurons showing strong immunoreactivity for 72,000 mol. wt heat shock protein in their perikarya and proximal processes. In addition, Golgi-like stained neurons with dystrophic features were occasionally observed in the ipsilateral substantia nigra pars reticulata. The immunoreactivity for 72,000 mol. wt heat shock protein in the ipsilateral pars reticulata gradually declined and almost disappeared by 15 days after transection. No apparent induction of 72,000 mol. wt heat shock protein was found in the substantia nigra pars compacta throughout the time period examined. Massive striatal ischemic injury produced by transient middle cerebral artery occlusion also induced expression of 72,000 mol. wt heat shock protein in the pars reticulata neurons three and four days postoperatively. These findings suggest that deafferentation of the striatal or striatopallidal inputs per se is a harmful stress for the substantia nigra pars reticulata neurons, inducing 72,000 mol. wt heat shock protein synthesis. The present data may contribute to our understanding of the molecular basis of the pathomechanism of the transneuronal regression of substantia nigra pars reticulata neurons, which may occur after removal of inhibitory GABAergic inputs.
黑质接受来自纹状体和苍白球的大量抑制性γ-氨基丁酸能投射纤维支配，其传入神经切断被认为会导致黑质神经元顺行性跨突触变性。采用免疫组织化学方法检测大脑半横断或短暂大脑中动脉闭塞后黑质中72,000分子量热休克蛋白的诱导情况。在横断后3天和4天，在同侧黑质网状部发现了对72,000分子量热休克蛋白的强免疫反应性。光镜观察显示，许多网状部神经元在其胞体和近端突起中对72,000分子量热休克蛋白表现出强免疫反应性。此外，在同侧黑质网状部偶尔观察到具有营养不良特征的高尔基样染色神经元。同侧网状部中72,000分子量热休克蛋白的免疫反应性逐渐下降，横断后15天几乎消失。在所检查的整个时间段内，黑质致密部未发现72,000分子量热休克蛋白的明显诱导。短暂大脑中动脉闭塞引起的大量纹状体缺血性损伤也在术后3天和4天诱导了网状部神经元中72,000分子量热休克蛋白的表达。这些发现表明，纹状体或纹状体苍白球输入的传入神经切断本身对黑质网状部神经元是一种有害应激，可诱导72,000分子量热休克蛋白的合成。本研究数据可能有助于我们理解黑质网状部神经元跨神经元退变发病机制的分子基础，这种退变可能在去除抑制性γ-氨基丁酸能输入后发生。
