Aberrant Adult Neurogenesis in the Subventricular Zone-Rostral Migratory Stream-Olfactory Bulb System Following Subchronic Manganese Exposure
Aberrant Adult Neurogenesis in the Subventricular Zone-Rostral Migratory Stream-Olfactory Bulb System Following Subchronic Manganese Exposure
复制标题
DOI：
10.1093/toxsci/kfw007
复制
发表时间：
2016-04-01
影响因子：
3.8
通讯作者：
Zheng, Wei
中科院分区：
文献类型：
--
作者：
Fu, Sherleen;Jiang, Wendy;Zheng, Wei
成体神经发生发生在脑室下区（SVZ）。我们最近的数据显示，大鼠亚慢性锰（Mn）暴露后，SVZ中BrdU（+）细胞增殖增加。本研究旨在区分锰对成年神经发生的关键阶段，即增殖，迁移，生存和分化从SVZ通过吻迁移流到嗅球（OB）的影响。成年大鼠在4周Mn暴露结束时接受单次IP剂量的BrdU以标记增殖细胞。免疫组织化学染色和细胞计数显示，锰暴露组SVZ中BrdU（+）细胞比对照组增加48%（P <0.05）。这些BrdU（+）细胞被鉴定为主要为GFAP（+）B型神经干细胞、Nestin（+）C型转运祖细胞、DCX（+）迁移性成神经细胞和Iba 1（+）小胶质细胞的混合群体。另一组成年大鼠每天接受3次BrdU ip注射，随后进行亚慢性Mn暴露。BrdU标记后4周，OB中大部分存活的BrdU（+）细胞分化为NeuN（+）成熟神经元。然而，锰暴露组和对照组OB中BrdU/NeuN/DAPI三重标记细胞的存活率分别为33%和64%（P <0.01）。铜直接注入侧脑室显著降低SVZ细胞增殖。总之，这些结果表明，锰暴露最初增强了成人SVZ中的细胞增殖。然而，在OB中，Mn暴露显著减少存活的成体细胞，并显著抑制其分化为成熟神经元，导致OB中的成体神经发生总体减少。
Adult neurogenesis occurs in brain subventricular zone (SVZ). Our recent data reveal an elevated proliferation of BrdU(+) cells in SVZ following subchronic manganese (Mn) exposure in rats. This study was designed to distinguish Mn effect on the critical stage of adult neurogenesis, ie, proliferation, migration, survival and differentiation from the SVZ via the rostral migratory stream to the olfactory bulb (OB). Adult rats received a single ip-dose of BrdU at the end of 4-week Mn exposure to label proliferating cells. Immunostaining and cell-counting showed a 48% increase of BrdU(+) cells in Mn-exposed SVZ than in controls (P < .05). These BrdU(+) cells were identified as a mixed population of mainly GFAP(+) type-B neural stem cells, Nestin(+) type-C transit progenitor cells, DCX(+) migratory neuroblasts and Iba1(+) microglial cells. Another group of adult rats received 3 daily ip-injections of BrdU followed by subchronic Mn exposure. By 4-week post BrdU labeling, most of the surviving BrdU(+) cells in the OB were differentiated into NeuN(+) matured neurons. However, survival rates of BrdU/NeuN/DAPI triple-labeled cells in OB were 33% and 64% in Mn-exposed and control animals, respectively (P < .01). Infusion of Cu directly into the lateral ventricle significantly decreased the cell proliferation in the SVZ. Taken together, these results suggest that Mn exposure initially enhances the cell proliferation in adult SVZ. In the OB, however, Mn exposure significantly reduces the surviving adult-born cells and markedly inhibits their differentiation into mature neurons, resulting in an overall decreased adult neurogenesis in the OB.