title: The presenilin-1 familial Alzheimer's disease mutation P117L decreases neuronal differentiation of embryonic murine neural progenitor cells.
abstract: The presenilin-1 gene is mutated in early-onset familial Alzheimer's disease. The mutation Pro117Leu is implicated in a very severe form of the disease, with an onset of less than 30 years. The consequences of this mutation on neurogenesis in the hippocampus of adult transgenic mice have already been studied in situ. The survival of neural progenitor cells was impaired resulting in decreased neurogenesis in the dentate gyrus. Our intention was to verify if similar alterations could occur in vitro in progenitor cells from the murine ganglionic eminences isolated from embryos of this same transgenic mouse model. These cells were grown in culture as neurospheres and after differentiation the percentage of neurons generated as well as their morphology were analysed. The mutation results in a significant decrease in neurogenesis compared to the wild type mice and the neurons grow longer and more ramified neurites. A shift of differentiation towards gliogenesis was observed that could explain decreased neurogenesis despite increased proliferation of neural precursors in transgenic neurospheres. A diminished survival of the newly generated mutant neurons is also proposed. Our data raise the possibility that these alterations in embryonic development might contribute to increase the severity of the Alzheimer's disease phenotype later in adulthood.
authors: Department of Fundamental Neuroscience, University of Geneva School of Medicine, Geneva University, CH-1211 Geneva, Switzerland. lorenza.eder@bluemail.ch
authors: Lorenza
authors: L
authors: Eder-Colli
authors: Noelia
authors: N
authors: Abad-Estarlich
authors: Carine
authors: C
authors: Pannetier
authors: Philippe G
authors: PG
authors: Vallet
authors: Claude
authors: C
authors: Walzer
authors: Gregory A
authors: GA
authors: Elder
authors: Nikolaos K
authors: NK
authors: Robakis
authors: Constantin
authors: C
authors: Bouras
authors: Armand
authors: A
authors: Savioz
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053764:Presenilin-1