老年F344大鼠黑质中铁沉积的研究

STUDY OF IRON DEPOSITION IN THE SUBSTANTIA NIGRA OF AGED F344 RATS

脑内一些区域的胶质细胞中铁过多沉积和由铁介导的“氧化应激反应”可能与 Parkinson病 (PD)等神经退行性疾病的发病有关。但目前对老年 F 3 44大鼠中脑黑质铁沉积的亚细胞结构研究报道还不多。本研究选用老年 (2 4个月 ) Fischer (F3 44)大鼠 ,采用免疫组织化学、激光共聚焦显微镜、透射电子显微镜及电子探针元素能量微分析等技术 ,对中脑黑质部位铁的沉积进行了形态学观察。结果显示 :在光镜下 ,作为铁的主要储存形式 -铁结合蛋白在黑质网状部有明显增加并伴有小胶质细胞的增加 ;激光共聚焦显微镜观察到它们很少存在于多巴胺神经元及星形胶质细胞而主要存在于小胶质细胞中 ;利用电子探针检测显示游离铁元素主要存在于星形胶质细胞的胞浆内 ,也在小胶质细胞、少突胶质细胞及部分神经元的胞浆内发现有铁元素沉积。本文作者认为 :随年龄的增长 ,黑质中小胶质细胞增加可能是铁在黑质中沉积的原因之一 ,后者引起的自由基化增加所导致的老年神经系统的氧化损伤 ,可能是导致

Increase of iron-laden glia in the specific regions of aged brain and iron-mediated oxidative stress may be of pathogenic significance for the development of Parkinson's Disease (PD) and other neurodegenerative disorders. However, the cellular distribution, especially the ultrastructure localization for iron deposition in the aged Fischer F344 rat substantia nigra (SN) is ambiguous. In the present study, immunohistochemistry, laser scanning confocal microscopy, transmission electron microscopy and elemental microanalytical techniques (electron microprobe) were used to demonstrate the existence of iron-laden cells in the SN of aged (24 months) F344 rats. The results revealed that there was a concurrent increase in the number of ferrintin positive cells and microglia cells in the SN. Laser scanning confocal microscopy showed that ferrintin immunoreactivity is primarily co-localized with OX42 positive microglial cells instead of other type of cells in the SN. Iron elements was detected in the inclusions of astrocytes, microglia cells, oligodendrocytes and neurons in the SN by electron microprobe analysis. The present study suggests that the increasing of microglial cells in the SN with aging may be involved in the iron accumulation in the SN. Therefore, the iron-mediated free radical increases in the SN may be responsible for PD increasing in aging.