Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment

Xue Feng Ding, Xiang Gao, Xin Chun Ding, Ming Fan, Jinhui Chen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number25780
JournalScientific Reports
Volume6
DOIs
StatePublished - May 13 2016

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Dendrites
Hippocampus
Neurons
Neuronal Plasticity
Morphogenesis
Intellectual Disability
Dementia
Retroviridae
Nervous System Diseases
Brain

ASJC Scopus subject areas

  • General

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Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment. / Ding, Xue Feng; Gao, Xiang; Ding, Xin Chun; Fan, Ming; Chen, Jinhui.

In: Scientific Reports, Vol. 6, 25780, 13.05.2016.

Research output: Contribution to journalArticle

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