Differential responses of endogenous adult mouse neural precursors to excess neuronal excitation.

Differential responses of endogenous adult mouse neural precursors to excess neuronal excitation.
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内源性成年小鼠神经前体对过度神经元兴奋的差异反应。

DOI:
10.1111/j.1460-9568.2012.08244.x
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发表时间:
2012
期刊:
影响因子:
3.4
通讯作者:
Yamada H.
Yamada H.
中科院分区:
医学3区
文献类型:
--
作者:
Mori T;Wakabayashi T;Hirahara Y;Takamori Y;Koike T;Kurokawa K;Yamada H.

文献摘要

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海马颗粒下区 (SGZ) 的成人神经发生会因过度和轻微的神经元兴奋而增强,例如化学惊厥引起的短暂癫痫发作。由于大多数癫痫发作后神经发生的研究都集中在 SGZ,因此增强室下区 (SVZ) 神经发生所需的神经元兴奋阈值尚不清楚。因此,我们检查了 SVZ 前体对单次给予化疗惊厥药戊四唑 (PTZ) 引起的短暂全身阵挛发作的反应。通过全身施用胸苷类似物来分析前体的细胞周期进程。我们发现短暂的癫痫发作立即导致 SVZ 细胞周期延迟。然而,在SGZ却没有看到同样的效果。 SVZ 中最初的细胞周期延迟随后是第一轮有丝分裂后细胞周期重新进入的增强,导致前体池扩张,但细胞周期延迟和前体池的扩张是短暂的。 PTZ 治疗组的细胞周期进展在一个细胞周期后恢复正常。癫痫发作后 2 天以上,SVZ 前体细胞和嗅球中新神经元(SVZ 前体细胞的后代)的数量与对照小鼠的数量没有显着差异。由于在电惊厥发作后观察到类似的效果,因此这些反应可能是短暂癫痫发作的一般效果。这些结果表明,与 SGZ 相比,SVZ 中的神经发生受到更严格的调控,并且需要更强的刺激来进行修改。
Adult neurogenesis in the subgranular zone of the hippocampus (SGZ) is enhanced by excess as well as mild neuronal excitation, such as chemoconvulsant‐induced brief seizures. Because most studies of neurogenesis after seizures have focused on the SGZ, the threshold of neuronal excitation required to enhance neurogenesis in the subventricular zone (SVZ) is not clear. Therefore, we examined the responses of SVZ precursors to brief generalized clonic seizures induced by a single administration of the chemoconvulsant pentylenetetrazole (PTZ). Cell cycle progression of precursors was analysed by systemic administration of thymidine analogues. We found that brief seizures immediately resulted in cell cycle retardation in the SVZ. However, the same effect was not seen in the SGZ. This initial cell cycle retardation in the SVZ was followed by enhanced cell cycle re‐entry after the first round of mitosis, leading to precursor pool expansion, but the cell cycle retardation and expansion of the precursor pool were transient. Cell cycle progression in the PTZ‐treated group returned to normal after one cell cycle. The numbers of precursors in the SVZ and new neurons in the olfactory bulb, which are descendants of SVZ precursors, were not significantly different from those in control mice more than 2 days after seizures. Because similar effects were observed following electroconvulsive seizures, these responses are likely to be general effects of brief seizures. These results suggest that neurogenesis in the SVZ is more tightly regulated and requires stronger stimuli to be modified than that in the SGZ.