Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment
Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment
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出生后齿状回神经祖细胞中的 Notch1 缺陷会导致情绪和认知障碍。
DOI：
10.1096/fj.201700216rr
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发表时间：
2017-10-01
期刊：
影响因子：
4.8
通讯作者：
Wu, Haitao
中科院分区：
文献类型：
--
作者：
Feng, Shufang;Shi, Tianyao;Wu, Haitao
众所周知，Notch1信号在胚胎神经发育和成人神经发生中起着至关重要的作用。最新证据表明，Notch1在成熟海马神经元突触可塑性中也起着关键作用。到目前为止，对Notch1信号在成人神经发生不同阶段的功能仍缺乏更深入的了解，Notch1功能障碍与脑部疾病相关的机制也知之甚少。在本研究中，我们发现Notch1在海马齿状回成体未成熟神经元中高表达。通过双皮质素（DCX）（+）神经元特异性proopiomelanocortin (POMC)- α Cre小鼠与固定的Notch1小鼠杂交，采用遗传方法选择性地切除出生后海马晚期未成熟前体中的Notch1信号，我们证实了Notch1信号在齿状回成年新生儿神经元的存活和功能中的关键作用。此外，行为学和功能研究表明，POMC-Notch1（-/-）突变小鼠表现出焦虑和抑郁样行为，齿状回突触传递特性受损。最后，我们的机制研究显示，Notch1突变体中cAMP反应元件结合蛋白（CREB）的磷酸化显著受损，这表明Notch1突变体的功能障碍与出生后生成的齿状回未成熟神经元中pCREB信号通路的中断有关。-冯顺，史，谭，邱军，杨辉，吴，燕，周伟，王伟，吴，华。出生后齿状回神经祖细胞Notch1缺失导致情绪和认知障碍。
It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX)(+) neuron-specific proopiomelanocortin (POMC)-alpha Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1(-/-) mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus.-Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.