Presenilin-1 Dependent Neurogenesis.pdf (7.01 MB)
Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory
journal contribution
posted on 2016-01-28, 00:00 authored by JA Bonds, Y. Kuttner-Hirshler, N. Bartolotti, MK Tobin, M. Pizzi, R. Marr, O. LazarovPresenilin-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.
Funding
: 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).
History
Publisher Statement
This is the copy of an article published in PLoS ONE © 2015 Public Library of Science Publications. : © 2015 Bonds et al.Publisher
Public Library of Scienceissn
1932-6203Issue date
2015-06-22Usage metrics
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