Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: Evaluation using adult mice treated with trimethyltin chloride as a model
Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: Evaluation using adult mice treated with trimethyltin chloride as a model
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DOI：
10.1002/jnr.20678
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Yoneda, Y
中科院分区：
文献类型：
--
作者：
Ogita, K;Nishiyama, N;Yoneda, Y
已知成年动物的海马齿状回含有神经祖细胞，其响应于脑损伤而增殖并分化成神经元。然而，很少有人观察到直接损伤的齿状回颗粒细胞层的再生。使用三甲基锡（TMT）治疗的小鼠作为体内模型，我们评估了这一层的能力，损伤后再生。TMT的管理诱导神经元死亡的齿状回选择性2天后，与恢复的颗粒神经元在第14天及以后。在TMT处理损伤后的早期阶段（2-5天），5-溴-2 '-脱氧尿苷（BrdU）掺入到齿状回中至少两种不同类型的细胞中：BrdU阳性/神经元核抗原（NeuN）阴性细胞主要见于颗粒下区和颗粒细胞层，而BrdU阳性/NeuN阳性细胞在齿状分子层和门中大量存在。此外，在治疗后的早期阶段，作为增殖细胞和神经祖细胞/神经元前体的标志物的增殖细胞核抗原、巢蛋白、NeuroD 3和doublecortin的表达在齿状回中极度增强。双染显示BrdU与巢蛋白和doublecortin共定位于颗粒下带。行为分析显示，TMT引起的认知障碍在治疗后第14天得到改善。总之，我们的数据表明，海马齿状回本身是能够再生的神经元细胞层，通过快速增强损伤后的神经发生。(c)2005 Wiley-Liss，Inc.
The hippocampal dentate gyrus in adult animals is known to contain neural progenitors that proliferate and differentiate into neurons in response to brain injury. Little has been observed, however, on regeneration of the granule cell layer of the dentate gyrus that has been directly injured. Using trimethyltin (TMT)-treated mice as an in vivo model, we evaluated the ability of this layer to regenerate after injury. The administration of TMT induced neuronal death in the dentate gyrus selectively 2 days later, with recovery of granule neurons on day 14 and thereafter. At an early stage (days 2-5) after the damage by TMT treatment, 5-bromo-2'-deoxyuridine (BrdU) incorporation into at least two different types of cells was facilitated in the dentate gyrus: BrdU-positive/neuronal nuclear antigen (NeuN)-negative cells were found predominantly in the subgranular zone and granule cell layer, whereas BrdU-positive/NeuN-positive cells were numerous in the dentate molecular layer and hilus. In addition, expression of proliferating cell nuclear antigen, nestin, NeuroD3, and doublecortin, which are markers for proliferating cells and neural progenitors/neuronal precursors, was extremely enhanced in the dentate gyrus at the early stage after treatment. Double staining revealed that BrdU was colocalized with nestin and doublecortin in the subgranular zone. Behavioral analysis revealed that TMT-induced cognition impairment was ameliorated by day 14 after the treatment. Taken together, our data indicate that the hippocampal dentate gyrus itself is capable of regenerating the neuronal cell layer through rapid enhancement of neurogenesis after injury. (c) 2005 Wiley-Liss, Inc.