Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer's Disease
| Autor: | Karl J.L. Fernandes, Sarah Petryszyn, Martin Parent, Frédéric Calon, Martin Dufresne, Anne Aumont, Sandra E. Joppé, Pierre Chaurand, Laura K. Hamilton, Alexandra Furtos, Fanie Barnabé-Heider |
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| Rok vydání: | 2014 |
| Předmět: |
Ependymal Cell
animal diseases Cell Biology Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Prosencephalon Neural Stem Cells Alzheimer Disease Genetics medicine Animals Regeneration Stem Cell Niche reproductive and urinary physiology 030304 developmental biology Cell Proliferation 0303 health sciences Fatty acid metabolism Cell growth Lipid metabolism Cell Biology Lipid Metabolism Microarray Analysis Neural stem cell nervous system diseases Cell biology Adult Stem Cells Disease Models Animal medicine.anatomical_structure nervous system chemistry Biochemistry Forebrain Molecular Medicine lipids (amino acids peptides and proteins) Autopsy 030217 neurology & neurosurgery Adult stem cell Oleic Acid |
| Zdroj: | Cell stem cell. 17(4) |
| ISSN: | 1875-9777 |
| Popis: | SummaryLipid metabolism is fundamental for brain development and function, but its roles in normal and pathological neural stem cell (NSC) regulation remain largely unexplored. Here, we uncover a fatty acid-mediated mechanism suppressing endogenous NSC activity in Alzheimer’s disease (AD). We found that postmortem AD brains and triple-transgenic Alzheimer’s disease (3xTg-AD) mice accumulate neutral lipids within ependymal cells, the main support cell of the forebrain NSC niche. Mass spectrometry and microarray analyses identified these lipids as oleic acid-enriched triglycerides that originate from niche-derived rather than peripheral lipid metabolism defects. In wild-type mice, locally increasing oleic acid was sufficient to recapitulate the AD-associated ependymal triglyceride phenotype and inhibit NSC proliferation. Moreover, inhibiting the rate-limiting enzyme of oleic acid synthesis rescued proliferative defects in both adult neurogenic niches of 3xTg-AD mice. These studies support a pathogenic mechanism whereby AD-induced perturbation of niche fatty acid metabolism suppresses the homeostatic and regenerative functions of NSCs. |
| Databáze: | OpenAIRE |
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