Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.
(2015) In Brain 138. p.440-455- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4908024
- author
- Richetin, Kevin ; Leclerc, Clémence ; Toni, Nicolas ; Gallopin, Thierry ; Pech, Stéphane ; Roybon, Laurent LU and Rampon, Claire
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Brain
- volume
- 138
- pages
- 440 - 455
- publisher
- Oxford University Press
- external identifiers
-
- pmid:25518958
- wos:000350209900030
- scopus:84922379340
- pmid:25518958
- ISSN
- 1460-2156
- DOI
- 10.1093/brain/awu354
- language
- English
- LU publication?
- yes
- id
- 0b663451-fc99-499d-8374-64187cb5ebda (old id 4908024)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25518958?dopt=Abstract
- date added to LUP
- 2016-04-01 11:00:35
- date last changed
- 2022-05-06 03:29:40
@article{0b663451-fc99-499d-8374-64187cb5ebda,
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.}},
author = {{Richetin, Kevin and Leclerc, Clémence and Toni, Nicolas and Gallopin, Thierry and Pech, Stéphane and Roybon, Laurent and Rampon, Claire}},
issn = {{1460-2156}},
language = {{eng}},
pages = {{440--455}},
publisher = {{Oxford University Press}},
series = {{Brain}},
title = {{Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.}},
url = {{http://dx.doi.org/10.1093/brain/awu354}},
doi = {{10.1093/brain/awu354}},
volume = {{138}},
year = {{2015}},
}