Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.

Details

Ressource 1Download: serval:BIB_845D28324E56.P001 (1825.88 [Ko])
State: Public
Version: author
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_845D28324E56
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.
Journal
Brain
Author(s)
Richetin K., Leclerc C., Toni N., Gallopin T., Pech S., Roybon L., Rampon C.
ISSN
1460-2156 (Electronic)
ISSN-L
0006-8950
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
138
Number
Pt 2
Pages
440-455
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
In adult mammals, neural progenitors located in the dentate gyrus retain their ability to generate neurons and glia throughout lifetime. In rodents, increased production of new granule neurons is associated with improved memory capacities, while decreased hippocampal neurogenesis results in impaired memory performance in several memory tasks. In mouse models of Alzheimer's disease, neurogenesis is impaired and the granule neurons that are generated fail to integrate existing networks. Thus, enhancing neurogenesis should improve functional plasticity in the hippocampus and restore cognitive deficits in these mice. Here, we performed a screen of transcription factors that could potentially enhance adult hippocampal neurogenesis. We identified Neurod1 as a robust neuronal determinant with the capability to direct hippocampal progenitors towards an exclusive granule neuron fate. Importantly, Neurod1 also accelerated neuronal maturation and functional integration of new neurons during the period of their maturation when they contribute to memory processes. When tested in an APPxPS1 mouse model of Alzheimer's disease, directed expression of Neurod1 in cycling hippocampal progenitors conspicuously reduced dendritic spine density deficits on new hippocampal neurons, to the same level as that observed in healthy age-matched control animals. Remarkably, this population of highly connected new neurons was sufficient to restore spatial memory in these diseased mice. Collectively our findings demonstrate that endogenous neural stem cells of the diseased brain can be manipulated to become new neurons that could allow cognitive improvement.
Pubmed
Web of science
Open Access
Yes
Create date
10/02/2015 14:30
Last modification date
25/09/2019 7:09
Usage data