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Publication : Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory.

First Author  Bonds JA Year  2015
Journal  PLoS One Volume  10
Issue  6 Pages  e0131266
PubMed ID  26098332 Mgi Jnum  J:237894
Mgi Id  MGI:5817326 Doi  10.1371/journal.pone.0131266
Citation  Bonds JA, et al. (2015) Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory. PLoS One 10(6):e0131266
abstractText  Presenilin-1 (PS1), the catalytic core of the aspartyl protease gamma-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 beta-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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