Conditional overexpression of insulin-like growth factor-1 enhances hippocampal neurogenesis and restores immature neuron dendritic processes after traumatic brain injury.
Conditional overexpression of insulin-like growth factor-1 enhances hippocampal neurogenesis and restores immature neuron dendritic processes after traumatic brain injury.
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DOI：
10.1097/nen.0000000000000092
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发表时间：
2014-08
影响因子：
3.2
通讯作者：
Saatman KE
中科院分区：
文献类型：
--
作者：
Carlson SW;Madathil SK;Sama DM;Gao X;Chen J;Saatman KE
创伤性脑损伤与海马区的神经元损伤或死亡有关，海马区是认知功能的关键区域。海马神经源性神经龛内的未成熟神经元特别容易受到脑外伤的影响。保护未成熟的海马神经元或促进创伤后神经再生的治疗策略可能有利于促进脑外伤后的功能恢复。胰岛素样生长因子-1(IGF-1)促进成人脑内神经发生，但其对脑外伤后神经发生的影响尚不清楚。我们使用一种星形胶质细胞特异性条件性IGF-1过度表达的小鼠模型，在受控皮质撞击损伤后神经元损伤和反应性星形胶质细胞增生的区域补充IGF-1。虽然早期未成熟神经元的丢失没有明显减轻，但在损伤后10d，IGF-1的过度表达导致颗粒下区未成熟神经元密度显著增加。这种延迟的增加似乎是由神经元分化增强而不是细胞增殖增加推动的。在野生型小鼠中，未成熟神经元树突的总长度和分叉数量在损伤后10天比假损伤小鼠显著减少。相反，脑损伤IGF-1过表达小鼠未成熟神经元树突的形态与假手术对照组相当。这些数据提供了令人信服的证据，证明IGF-1促进了脑外伤后的神经发生。
Traumatic brain injury (TBI) is associated with neuronal damage or death in the hippocampus, a region critical for cognitive function. Immature neurons within the hippocampal neurogenic niche are particularly susceptible to TBI. Therapeutic strategies that protect immature hippocampal neurons or enhance post-traumatic neurogenesis may be advantageous for promoting functional recovery after TBI. Insulin-like growth factor-1 (IGF-1) promotes neurogenesis in the adult brain, but its effects on neurogenesis after TBI are unknown. We used an astrocyte-specific conditional IGF-1-overexpressing mouse model to supplement IGF-1 in regions of neuronal damage and reactive astrocytosis following controlled cortical impact injury. Although early loss of immature neurons was not significantly attenuated, overexpression of IGF-1 resulted in a marked increase in immature neuron density in the subgranular zone at 10 days post-injury. This delayed increase appeared to be driven by enhanced neuron differentiation rather than increased cellular proliferation. In wild type mice, dendrites of immature neurons exhibited significant decreases in total length and numbers of bifurcations at 10 days post-injury vs. neurons in sham-injured mice. In contrast, the morphology of immature neuron dendrites in brain-injured IGF-1-overexpressing mice was equivalent to that in sham controls. These data provide compelling evidence that IGF-1 promotes neurogenesis following TBI.