Temporally specified genetic ablation of neurogenesis impairs cognitive recovery after traumatic brain injury.
Temporally specified genetic ablation of neurogenesis impairs cognitive recovery after traumatic brain injury.
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DOI：
10.1523/jneurosci.5265-10.2011
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发表时间：
2011-03-30
期刊：
影响因子：
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通讯作者：
Kernie SG
中科院分区：
文献类型：
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作者：
Blaiss CA;Yu TS;Zhang G;Chen J;Dimchev G;Parada LF;Powell CM;Kernie SG
在基本上所有形式的严重脑损伤之后，都会发生显著的自发恢复，尽管这种恢复的机制尚不清楚。考虑到许多形式的脑损伤，如创伤性脑损伤(TBI)，都会诱导海马神经发生，我们研究了这些新产生的神经元是否可能在恢复过程中发挥作用。通过在转基因小鼠中建立脑损伤模型，我们确定了损伤诱导的新生成的神经元随着时间的推移而持续存在，并详细阐述了广泛的树突树，这些树稳定地整合在齿状回的所有神经元层。在nestin-HSV-TK转基因模型中，当我们在损伤时用更昔洛韦选择性地切除分裂的干/祖细胞时，我们消除了损伤诱导的神经发生，随后减少了祖细胞池。此外，使用海马区特定的行为测试，我们证明只有在损伤时被切除的神经发生损伤的动物才会失去学习空间记忆任务的能力。这些数据显示了脑损伤后成人神经发生的功能作用，并提供了令人信服和可测试的治疗方案，可能会促进康复。
Significant spontaneous recovery occurs following essentially all forms of serious brain injury, though the mechanisms underlying this recovery are unknown. Given that many forms of brain injury such as traumatic brain injury (TBI) induce hippocampal neurogenesis, we investigated whether these newly generated neurons might play a role in recovery. By modeling TBI in transgenic mice, we determined that injury-induced newly generated neurons persisted over time and elaborated extensive dendritic trees that stably incorporated themselves throughout all neuronal layers of the dentate gyrus. When we selectively ablated dividing stem/progenitors at the time of injury with ganciclovir in a nestin-HSV-TK transgenic model, we eliminated injury-induced neurogenesis and subsequently diminished the progenitor pool. Moreover, using hippocampal-specific behavioral tests, we demonstrated that only injured animals with neurogenesis ablated at the time of injury lost the ability to learn spatial memory tasks. These data demonstrate a functional role for adult neurogenesis following brain injury and offer compelling and testable therapeutic options that might enhance recovery.