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Overexpression of wild type but not an FAD mutant presenilin-1 promotes neurogenesis in the hippocampus of adult mice.

Mutations in the presenilin-1 (PS-1) gene are one cause of familial Alzheimer's disease (FAD). However, the functions of the PS-1 protein as well as how PS-1 mutations cause FAD are incompletely understood. Here we investigated if neuronal overexpression of wild-type or FAD mutant PS-1 in transgenic mice affects neurogenesis in the hippocampus of adult animals. We show that either a wild-type or an FAD mutant PS-1 transgene reduces the number of neural progenitors in the dentate gyrus. However, the wild-type, but not the FAD mutant PS-1 promoted the survival and differentiation of progenitors leading to more immature granule cell neurons being generated in PS-1 wild type expressing animals. These studies suggest that PS-1 plays a role in regulating neurogenesis in adult hippocampus and that FAD mutants may have deleterious properties independent of their effects on amyloid deposition.

Pubmed ID: 12079399

Authors

  • Wen PH
  • Shao X
  • Shao Z
  • Hof PR
  • Wisniewski T
  • Kelley K
  • Friedrich VL
  • Ho L
  • Pasinetti GM
  • Shioi J
  • Robakis NK
  • Elder GA

Journal

Neurobiology of disease

Publication Data

June 24, 2002

Associated Grants

  • Agency: NIA NIH HHS, Id: AG05138
  • Agency: NIA NIH HHS, Id: AG08200
  • Agency: NIA NIH HHS, Id: AG14392
  • Agency: NIA NIH HHS, Id: AG17926

Mesh Terms

  • Aging
  • Alzheimer Disease
  • Animals
  • Cell Count
  • Cell Differentiation
  • Cell Survival
  • Hippocampus
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Mutation
  • Neurons
  • Presenilin-1
  • Stem Cells