title: Amyloid-beta peptide affects viability but not differentiation of embryonic and adult rat hippocampal progenitor cells.
abstract: The neurological deficits that are characteristic of Alzheimer's Disease (AD) are ultimately a result of neuronal loss in distinct anatomical regions of the brain. This neuronal loss is thought to be due, in large part to the presence of the neurotoxic beta-amyloid (Abeta) deposits, that are characteristic of the AD brain. Transplantation therapy, in which neural stem cells (NSCs) or neural progenitor cells (NPCs) are introduced into damaged regions of the brain and induced to differentiate into replacement neurons, has been proposed as a possible therapeutic approach to treat AD. However, in the AD brain Abeta plaques, which remain in the area of neuronal degeneration, may affect the viability or differentiation potential of transplanted NSCs. Currently there is contradictory evidence concerning the effect of Abeta on NSCs. To further investigate the effect of Abeta on NSCs, we compared the mitochondrial function, proliferation and cellular differentiation of two populations of hippocampal NSCs (embryonic and adult derived) after Abeta exposure. Our results highlight the heterogeneity between different populations of NSCs even when derived from the same brain region. Our data also demonstrate that while mitochondrial function of NSCs is affected by Abeta, their proliferation and differentiation are not significantly influenced. Considered with previous studies, our results suggest that while NSCs do respond to the presence of Abeta, proliferation and differentiation of certain populations are not affected. Further study of the differences between susceptible vs. resistant populations of NSCs may provide crucial clues for the development of effective therapies to combat AD.
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: James N
authors.initials: JN
authors.lastname: Eucher
authors.forename: Etsuro
authors.initials: E
authors.lastname: Uemura
authors.forename: Donald S
authors.initials: DS
authors.lastname: Sakaguchi
authors.forename: M Heather West
authors.initials: MH
authors.lastname: Greenlee
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000166:cytology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D016229:Amyloid beta-Peptides; D000963:Antimetabolites; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D001973:Bromodeoxyuridine