Journal
EXPERIMENTAL NEUROLOGY
Volume 177, Issue 1, Pages 50-60Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/exnr.2002.7989
Keywords
neural stem cells; dopamine differentiation; tyrosine hydroxylase; transplantation; Parkinson's disease; 6-hydroxydopmine
Categories
Funding
- NINDS NIH HHS [NS 43309, R01 NS024204-11A2, R01 NS032519-09, R01 NS043309-02, R01 NS024204-10, NS32519, R01 NS032519-08, R01 NS043309-01, NS24204, R01 NS032519-07] Funding Source: Medline
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The ability to differentiate neural stem cells (NSCs) into dopamine neurons is fundamental to their role in cell replacement therapies for neurodegenerative disorders such as Parkinson's disease. We show here that when a clonal line (C17.2) of undifferentiated NSCs is transplanted into the intact or 6-hydroxydopaminelesioned striatum, cells withdraw from the cell cycle (BrdU-), migrate extensively in the host striatum, and express markers associated with neuronal (beta-tubulin III+, NSE+, NeuN(+)) but not glial (GFAP(-), MBP-, A2B5(-)) differentiation. Importantly, by 2-5 weeks postgrafting, in the majority of these transplants, nearly all engrafted cells express the dopamine-synthesizing enzymes tyrosine hydroxylase and aromatic L-amino decarboxylase, sometimes resulting in changes in motor behavior. In contrast, no NSCs stain for dopamine-phydroxylase, choline acetyltransferase, glutamic acid decarboxylase, or serotonin. We conclude that, following transplantation into the intact or 6-hydroxydopamine-lesioned rat, the adult brain contains intrinsic cues sufficient to direct the specific expression of dopaminergic traits in immature multipotential neural stem cells. (C) 2002 Elsevier Science (USA).
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