Jyothi H J, Vidyadhara D J, Mahadevan Anita, Philip Mariamma, Parmar Suresh Kumar, Manohari S Gowri, Shankar S K, Raju Trichur R, Alladi Phalguni Anand
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bengaluru, India.
Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bengaluru, India.
Neurobiol Aging. 2015 Dec;36(12):3321-3333. doi: 10.1016/j.neurobiolaging.2015.08.024. Epub 2015 Aug 31.
Age being a risk factor for Parkinson's disease, assessment of age-related changes in the human substantia nigra may elucidate its pathogenesis. Increase in Marinesco bodies, α-synuclein, free radicals and so forth in the aging nigral neurons are clear indicators of neurodegeneration. Here, we report the glial responses in aging human nigra. The glial numbers were determined on Nissl-stained sections. The expression of glial fibrillary acidic protein, S100β, 2', 3'-cyclic nucleotide 3' phosphodiesterase, and Iba1 was assessed on cryosections of autopsied midbrains by immunohistochemistry and densitometry. The glial counts showed a biphasic increase, of which, the first prominent phase from fetal age to birth could be physiological gliogenesis whereas the second one after middle age may reflect mild age-related gliosis. Astrocytic morphology was altered, but glial fibrillary acidic protein expression increased only mildly. Presence of type-4 microglia suggests possibility of neuroinflammation. Mild reduction in 2', 3'-cyclic nucleotide 3' phosphodiesterase-labeled area denotes subtle demyelination. Stable age-related S100β expression indicates absence of calcium overload. Against the expected prominent gliosis, subtle age-related morphological alterations in human nigral glia attribute them a participatory role in aging.
年龄是帕金森病的一个风险因素,评估人类黑质中与年龄相关的变化可能有助于阐明其发病机制。衰老的黑质神经元中马里内斯科小体、α-突触核蛋白、自由基等的增加是神经退行性变的明显指标。在此,我们报告衰老人类黑质中的胶质细胞反应。在尼氏染色切片上确定胶质细胞数量。通过免疫组织化学和光密度测定法,在尸检中脑的冰冻切片上评估胶质纤维酸性蛋白、S100β、2',3'-环核苷酸3'-磷酸二酯酶和离子钙结合衔接分子1的表达。胶质细胞计数呈双相增加,其中,从胎儿期到出生的第一个突出阶段可能是生理性胶质细胞生成,而中年后的第二个阶段可能反映轻度的年龄相关性胶质增生。星形胶质细胞形态发生改变,但胶质纤维酸性蛋白表达仅轻度增加。4型小胶质细胞的存在提示神经炎症的可能性。2',3'-环核苷酸3'-磷酸二酯酶标记区域的轻度减少表明存在细微的脱髓鞘。与年龄相关的S100β表达稳定表明不存在钙超载。与预期的明显胶质增生相反,人类黑质胶质细胞中与年龄相关的细微形态学改变表明它们在衰老过程中起参与作用。