Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the adult

Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the adult
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DOI:
10.1016/s0306-4522(97)00127-9
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发表时间:
1997-09-01
期刊:
影响因子:
3.3
通讯作者:
Tanapat, P
Tanapat, P
中科院分区:
医学3区
文献类型:
--
作者:
Gould, E;Tanapat, P

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为了确定颗粒细胞死亡是否刺激成年大鼠齿状回颗粒细胞前体细胞的增殖,我们对颗粒细胞层进行了兴奋性损伤和机械性损伤,并检测了不同存活时间的增殖细胞数量。采用[H-3]胸腺嘧啶核苷放射自显影、溴脱氧尿嘧啶核苷标记和增殖细胞核抗原免疫组织化学方法,观察到术后24 h损伤侧较健侧增殖细胞增多。颗粒细胞损伤程度与增殖细胞数呈显著正相关。结合[H-3]胸腺嘧啶核苷放射自显影和细胞特异性标志物的免疫组织化学显示,绝大多数增殖细胞具有颗粒细胞前体的形态特征,对未成熟胶质细胞的标志物波形蛋白不呈免疫反应。[H-3]胸腺嘧啶核苷放射自显影和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记相结合的退变细胞显示,增殖细胞不会迅速退变。损伤后3周,损伤后产生的细胞大多具有成熟颗粒神经元的形态特征,定位于颗粒细胞层,表达神经元特异性烯醇化酶、N-甲基-D-天冬氨酸受体亚单位NRI和Calbinine等成熟颗粒神经元的标志物,提示颗粒细胞死亡刺激前体细胞增殖,其中许多前体细胞存活并分化为成熟颗粒神经元。(C)1997年IBRO。爱思唯尔科学有限公司出版。
In order to determine whether granule cell death stimulates the proliferation of granule cell precursors in the dentate gyrus of the adult rat, we performed both excitotoxic and mechanical lesions of the granule cell layer and examined the numbers of proliferating cells at different survival times. Using [H-3]thymidine autoradiography, bromodeoxyuridine labelling and proliferating cell nuclear antigen immunohistochemistry, we observed an increase in proliferating cells on the lesioned side compared to the unlesioned side 24 h after surgery. A significant positive correlation between the extent of granule cell damage and the number of proliferating cells was observed. Combined [H-3]thymidine autoradiography and immunohistochemistry for cell-specific markers revealed that the vast majority of proliferating cells had the morphological characteristics of granule cell precursors and were not immunoreactive for vimentin, a marker of immature glia. Combined [H-3]thymidine autoradiography and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling for degenerating cells showed that the proliferating cells did not rapidly degenerate. Three weeks after the lesion, most cells produced in response to the lesion had the morphological characteristics of mature granule neurons, were located in the granule cell layer and expressed markers of mature granule neurons, including neuron-specific enolase, the N-methyl-D-aspartate receptor subunit NRI and calbindin.These findings suggest that granule cell death stimulates the proliferation of precursor cells, many of which survive and differentiate into mature granule neurons. (C) 1997 IBRO. Published by Elsevier Science Ltd.