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Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory

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posted on 28.01.2016 by JA Bonds, Y. Kuttner-Hirshler, N. Bartolotti, MK Tobin, M. Pizzi, R. Marr, O. Lazarov
Presenilin-1 (PS1), the catalytic core of the aspartyl protease γ-secretase, regulates adult neurogenesis. However, it is not clear whether the role of neurogenesis in hippocampal learning and memory is PS1-dependent, or whether PS1 loss of function in adult hippocampal neurogenesis can cause learning and memory deficits. Here we show that downregulation of PS1 in hippocampal neural progenitor cells causes progressive deficits in pattern separation and novelty exploration. New granule neurons expressing reduced PS1 levels exhibit decreased dendritic branching and dendritic spines. Further, they exhibit reduced survival. Lastly, we show that PS1 effect on neurogenesis is mediated via β-catenin phosphorylation and notch signaling. Together, these observations suggest that impairments in adult neurogenesis induce learning and memory deficits and may play a role in the cognitive deficits observed in Alzheimer’s disease.

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: This work was funded by the US National Institutes of Health grants RO1 AG033570, 1 RC1 AG036208-01, the Brain Research Foundation G- 2010-10 (OL), and 5 T32 HL 007692-24 (JAB).

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Publisher Statement

This is the copy of an article published in PLoS ONE © 2015 Public Library of Science Publications. : © 2015 Bonds et al.

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Public Library of Science

issn

1932-6203

Issue date

22/06/2015

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