The presenilin-1 familial Alzheimer's disease mutation P117L decreases neuronal differentiation of embryonic murine neural progenitor cells

Article Article scientifique Article The presenilin-1 familial Alzheimer's disease mutation P117L decreases neuronal differentiation of embryonic murine neural progenitor cells eng 2009 author Eder-Colli Lorenza author Abad-Estarlich Noelia author Pannetier Carine 514002 author Vallet Philippe 526543 author Walzer Claude 649968 author Elder Gregory A. author Robakis Nikolaos K. author Bouras Constantin 27275 author Savioz Armand 0000-0001-8059-8281 135243 296-301 10.1016/j.brainresbull.2009.06.007 19555743 0361-9230 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757516/pdf/nihms-126682.pdf 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. Alzheimer Disease/*genetics Animals Apoptosis/genetics Astrocytes/metabolism Cell Count Cells, Cultured Immunohistochemistry Mice Mice, Transgenic Multipotent Stem Cells/cytology Mutation Neurogenesis/*genetics Neurons/*cytology/metabolism Presenilin-1/*genetics Reverse Transcriptase Polymerase Chain Reaction Dewey 590 Dewey 616.89 44 Département de génétique et évolution 162 60 Département de psychiatrie 225 false 1 Groupe Bouras Constantin (neuropsychiatrie) 1 Brain research bulletin 80 4-5 38fd0f28-f209-4842-9244-372ec948d1a6 Article Restricted file1.pdf 309910 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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The presenilin-1 familial Alzheimer's disease mutation P117L decreases neuronal differentiation of embryonic murine neural progenitor cells	Brain research bulletin			2009	656	0

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Pannetier, Carine