Disruption of postnatal progenitor migration and consequent abnormal pattern of glial distribution in the cerebrum following administration of methylmercury
Disruption of postnatal progenitor migration and consequent abnormal pattern of glial distribution in the cerebrum following administration of methylmercury
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DOI：
10.1093/jnen/62.8.835
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发表时间：
2003-08-01
影响因子：
3.2
通讯作者：
Takahashi, H
中科院分区：
文献类型：
--
作者：
Kakita, A;Inenaga, C;Takahashi, H
经胎盘给予甲基汞（MeHg）可导致发育中的大脑皮层神经元迁移中断。然而，甲基汞对神经胶质祖细胞迁移的影响仍不清楚。为了理解这一点，我们进行了双重管理的甲基汞和5-溴-2-脱氧尿苷（BrdU）的新生大鼠幼崽出生后第2天（P2），当胶质细胞产生的祖细胞在脑室下区（SVZ）。在P28对一部分甲基汞处理的大鼠进行组织学检查，发现大脑的初级运动皮层或初级躯体感觉皮层的细胞结构或神经元计数均无明显异常。BrdU免疫组化显示标记细胞在皮质深层和两个区域的下层白色物质中异常积聚，其中定位了过量的星形胶质细胞（胶质细胞酸性蛋白或S-100 β免疫标记细胞）和少突胶质细胞（2 '，3'-环核苷酸3 '-磷酸水解酶标记细胞）。接下来，为了研究来自P2新生儿前脑SVZ的单个祖细胞的迁移，我们在体内用编码绿色荧光蛋白（GFP）的逆转录病毒标记它们，在施用甲基汞后，然后检查GFP标记的细胞在P28大脑中的分布模式。我们发现，标记细胞发育成星形胶质细胞和少突胶质细胞，并异常积聚在外侧白色物质以及邻近的外侧皮质和纹状体外侧的深层。因此，暴露于甲基汞在胶质细胞形成期诱导神经胶质细胞的不规则分布，出生后的祖细胞的异常迁移的后果。
Transplacental administration of methylmercury (MeHg) induces disruption of neuronal migration in the developing cerebral cortex. However, the effects of MeHg on glial progenitor migration remain unclear. To understand this, we performed double administration of MeHg and 5-bromo-2-deoxyuridine (BrdU) to neonatal rat pups on postnatal day 2 (P2), when glial cells are generated from progenitors in the subventricular zone (SVZ). Histopathological examination of a proportion of the MeHg-treated rats on P28 revealed no apparent abnormalities of cytoarchitecture or neuron count in either the primary motor or primary somatosensory cortex of the cerebrum. BrdU immunohistochemistry revealed abnormal accumulation of the labeled cells in the deeper layers of the cortices and underlying white matter of both areas, where an excessive number of astrocytes (glial fibrillary acidic protein- or S-100beta-immunolabeled cells) and oligodendrocytes (2',3'-cyclic-nucleotide 3'-phosphohydrolase-labeled cells) were located. Next, to investigate the migration of individual progenitors from the forebrain SVZ of P2 neonates, we labeled them in vivo with a retrovirus encoding green fluorescent protein (GFP), following administration of MeHg, and then examined the distribution pattern of the GFP-labeled cells in the P28 cerebrum. We found that the labeled cells developed into astrocytes and oligodendrocytes and were accumulated abnormally in the lateral white matter as well as in the adjacent deeper layer of the lateral cortex and lateral side of the striatum. Thus, exposure to MeHg in the gliogenic period induced irregular distribution of glia as, a consequence of abnormal migration of the postnatal progenitors.