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The Journal of Neuroscience, October 13, 2004, 24(41):8924-8931; doi:10.1523/JNEUROSCI.2344-04.2004
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Neurobiology of Disease
Intrastriatal Transforming Growth Factor  Delivery to a Model of Parkinson's Disease Induces Proliferation and Migration of Endogenous Adult Neural Progenitor Cells without Differentiation into Dopaminergic Neurons
Oliver Cooper1 and
Ole Isacson1,2
1Harvard University and McLean Hospital, National Institute of Neurological Disorders and Stroke Udall Parkinson's Disease Research Center of Excellence, Belmont, Massachusetts 02478, and 2Department of Neurology and Program of Neuroscience, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, Boston, Massachusetts 02115
We examined the cell proliferative, neurogenic, and behavioral effects of transforming growth factor  (TGF) in a 6-OHDA Parkinson's disease model when compared with naive rats. Intrastriatal TGF infusion induced significant proliferation, hyperplastic nodules, and substantial migratory waves of nestin-positive progenitor cells from the adult subventricular zone (SVZ) of dopamine-denervated rats. Interestingly, SVZ cells in naive rats displayed proliferation but minimal migration in response to the TGF infusion. The cells in the expanded SVZ accumulated cytoplasmic  -catenin, indicating activation of classical Wnt signaling. However, no evidence of any neuronal differentiation was found of these recruited progenitor cells anywhere examined in the brain. Consequently, no evidence of dopaminergic (DA) neurogenesis was found in the striatum or substantia nigra in any experimental group, and amphetamine-induced behavioral rotations did not improve. In summary, the cells in the TGF-induced migratory cellular wave remain undifferentiated and do not differentiate into midbrain-like DA neurons.
Key words: TGF; dopaminergic; neural progenitor; Parkinson's disease; subventricular zone; infusion
Received June 15, 2004;
revised August 25, 2004;
accepted August 27, 2004.
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