Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru, 560029, India.
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru, 560029, India.
J Chem Neuroanat. 2019 Apr;97:57-65. doi: 10.1016/j.jchemneu.2019.02.001. Epub 2019 Feb 8.
The protein α-synuclein, a major component of Lewy bodies in nigral neurons of aged and Parkinson's disease (PD) patients, normally co-localizes with synaptophysin and regulates the pool of synaptic vesicles. Our earlier study on substantia nigra pars compacta (SNpc) in an Asian-Indian population, demonstrated an age-associated linear but non-logarithmic increase in soluble α-synuclein without any loss of nigral neurons. Another distinctive finding was the presence of activated microglia in the ventrolateral region of the aged nigra, suggesting sub-threshold neurodegeneration. Since microglia prune dendrites, we evaluated the alterations in dendritic arborisation in the SNpc from autopsied midbrains of Asian-Indians through aging, using Golgi-Kopsch protocol. Further, we evaluated the expression of synaptic proteins, synaptophysin and synaptotagmin-11 as parallel markers of synaptic transmission anomalies. The dendritic arborization pattern was typical of large multipolar neurons. A subtle but non-significant decline in parameters like dendritic length and number of intersections was noted. Thus, the alterations were milder than those reported in PD. In the neurons of the young (till 10 years), faint cytoplasmic immunoreactivity of synaptic proteins was noted. In the adults and elderly, it was membrane-bound or appeared as punctae within neuropil. Both proteins showed a slight age-related decline, suggesting a mild decrease in the synaptic vesicular traffic, affecting the dopamine transmission with age that may manifest as minor motor disabilities in the elderly. Mapping the differences in synaptic profiles in differentially susceptible ethnic populations, could reveal interesting insights. Thus, nigra of aged individuals and PD patients share pathogenic features that differ in magnitude.
α-突触核蛋白是老年和帕金森病（PD）患者黑质神经元路易小体的主要成分，通常与突触小泡蛋白共定位并调节突触小泡池。我们之前对亚洲-印度人群的黑质致密部（SNpc）进行的研究表明，可溶性α-突触核蛋白呈年龄相关的线性但非对数增加，而黑质神经元没有丢失。另一个独特的发现是，老化的黑质腹外侧区域存在激活的小胶质细胞，表明存在亚阈值神经退行性变。由于小胶质细胞修剪树突，我们通过老化，使用高尔基-科普施（Golgi-Kopsch）方案评估了尸检中脑 SNpc 中树突分支的变化。此外，我们评估了突触蛋白突触小泡蛋白和突触结合蛋白-11 的表达，作为突触传递异常的平行标志物。树突分支模式是大型多极神经元的典型特征。注意到树突长度和交点数量等参数略有但无统计学意义的下降。因此，这些变化比 PD 中报道的变化更为温和。在年轻（10 岁以内）的神经元中，突触蛋白的细胞质免疫反应较弱。在成年和老年个体中，它是膜结合的或在神经间质中呈现为点状。两种蛋白质都表现出轻微的年龄相关性下降，表明突触小泡运输略有减少，这会影响多巴胺传递，随着年龄的增长，可能会导致老年人出现轻微的运动障碍。对不同易感性种族人群的突触谱差异进行映射，可能会揭示出有趣的见解。因此，老化个体和 PD 患者的黑质具有不同程度的致病特征。
