Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory
Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory
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DOI：
10.1038/sj.jcbfm.9600153
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发表时间：
2005-12-01
影响因子：
6.3
通讯作者：
von Euler, G
中科院分区：
文献类型：
--
作者：
Bendel, O;Bueters, T;von Euler, G
海马CA1区的锥体神经元对空间学习和记忆等认知功能至关重要，在脑缺血后被选择性破坏。为了分析退化的CA1神经元是否被新神经元所取代，以及这种再生是否与学习和记忆缺陷的改善有关，我们使用了大鼠全脑缺血模型，该模型在缺血两周后提供了与空间学习和记忆的严重损伤相关的CA1神经元几乎完全消失（约为对照组的3%）。我们发现短暂性脑缺血可以引起CA1区域大量新神经元的形成，在缺血后90天（DAI）达到原始神经元数量的约40%。CA1中成熟神经元标记物神经元核与5-溴-2'-脱氧尿苷的共定位证实了缺血损伤后确实发生了神经发生。此外，我们发现在邻近侧脑室周围区域表达未成熟神经元标记物多唾液酸神经元细胞粘附分子的细胞数量增加，表明新形成的神经元来源于该区域。CA1神经元的重新出现与90 DAI缺血诱导的空间学习和记忆损伤的恢复有关，这表明新形成的CA1神经元恢复了海马CA1功能。总之，这些结果表明，大脑在损伤后具有内源性形成新神经细胞的能力，这与大脑认知功能的恢复有关。
The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.