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Amyotrophic lateral sclerosis (ALS) is a fatal adult human disease caused by motor neuron degeneration. Stem cell therapy might be a treatment for ALS. The adult mammalian forebrain has neural stem cells (NSCs) and neural progenitor cells (NPCs) in the anterior subventricular zone (SVZa), rostral migratory stream (RMS), olfactory bulb (OB) core, and dentate gyrus (DG). These cells could be used to rescue or replace degenerating upper and lower motor neurons through endogenous recruitment or autologous/allogenic transplantation. We evaluated the competency of forebrain NSCs and NPCs in transgenic (tg) mice harboring human mutant superoxide dismutase-1 (mSOD1), a model of ALS. Tg human wild-type SOD1 (wtSOD1) mice and non-tg mice were controls. Bromodeoxyuridine (BrdU) labeling of cells, a marker for cell proliferation and other events, was reduced in a niche-specific pattern in presymptomatic and symptomatic mice, with the SVZa having greater reductions than the RMS, OB, and DG. Different NSC and NPC complements were evaluated by localizing nestin, neural cell adhesion molecule, distalless-2 transcription factor, vimentin, and glial fibrillary acidic protein. In symptomatic mice, NSC markers were reduced, whereas NPC markers were unchanged or elevated. Neurogenesis was preserved in symptomatic mSOD1 mice. NSC/NPC competence assessment in vitro revealed that mSOD1 SVZa cells had the ability to proliferate and form neurospheres but had an impaired response to mitogen stimulation. We conclude that adult mSOD1 ALS mice have abnormalities in forebrain NSCs, but the essential features of NSC/NPCs remained in presymptomatic and symptomatic mice.
Pubmed ID: 16736475 RIS Download
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This monoclonal targets Neural Cell Adhesion Molecule
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets Chemical BrdU
View all literature mentionsThis polyclonal targets Glutamic Acid Decarboxylase 65/67
View all literature mentionsThis polyclonal targets Vimentin
View all literature mentionsThis monoclonal targets Bromodeoxyuridine (BrdU)
View all literature mentionsThis monoclonal targets Nestin
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