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Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory.

PloS one | 2015

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.

Pubmed ID: 26098332 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: 1 RC1 AG036208-01
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007692
  • Agency: NIA NIH HHS, United States
    Id: R01 AG033570
  • Agency: NIA NIH HHS, United States
    Id: RC1 AG036208
  • Agency: NHLBI NIH HHS, United States
    Id: 5 T32 HL 007692-24

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RRID:IMSR_JAX:000664

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