Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment.
Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment.
复制标题
Notch信号的产后失调会破坏海马中成年神经元的树突发展，并导致记忆障碍。
DOI：
10.1038/srep25780
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发表时间：
2016-05-13
影响因子：
4.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Ding XF;Gao X;Ding XC;Fan M;Chen J
Deficits in the Notch pathway are involved in a number of neurologic diseases associated with mental retardation or/and dementia. The mechanisms by which Notch dysregulation are associated with mental retardation and dementia are poorly understood. We found that Notch1 is highly expressed in the adult-born immature neurons in the hippocampus of mice. Retrovirus mediated knockout of notch1 in single adult-born immature neurons decreases mTOR signaling and compromises their dendrite morphogenesis. In contrast, overexpression of Notch1 intracellular domain (NICD), to constitutively activate Notch signaling in single adult-born immature neurons, promotes mTOR signaling and increases their dendrite arborization. Using a unique genetic approach to conditionally and selectively knockout notch 1 in the postnatally born immature neurons in the hippocampus decreases mTOR signaling, compromises their dendrite morphogenesis, and impairs spatial learning and memory. Conditional overexpression of NICD in the postnatally born immature neurons in the hippocampus increases mTOR signaling and promotes dendrite arborization. These data indicate that Notch signaling plays a critical role in dendrite development of immature neurons in the postnatal brain, and dysregulation of Notch signaling in the postnatally born neurons disrupts their development and thus contributes to the cognitive deficits associated with neurological diseases.
