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PMID: 15483111 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Intrastriatal transforming growth factor alpha delivery to a model of Parkinson's disease induces proliferation and migration of endogenous adult neural progenitor cells without differentiation into dopaminergic neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 24 ·No. 41 ·2004-10-13 ·Pages 8924-31

Cooper O, Isacson O

Abstract

We examined the cell proliferative, neurogenic, and behavioral effects of transforming growth factor alpha (TGFalpha) in a 6-OHDA Parkinson's disease model when compared with naive rats. Intrastriatal TGFalpha 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 TGFalpha infusion. The cells in the expanded SVZ accumulated cytoplasmic beta-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 TGFalpha-induced migratory cellular wave remain undifferentiated and do not differentiate into midbrain-like DA neurons.

MeSH Terms
Animals Behavior, Animal/drug effects Bromodeoxyuridine Cell Movement/drug effects Cell Proliferation/drug effects Corpus Striatum/drug effects,pathology Cytoskeletal Proteins/metabolism Disease Models, Animal Dopamine/metabolism Drug Administration Routes Intermediate Filament Proteins/biosynthesis Lateral Ventricles/cytology,drug effects,metabolism Male Nerve Tissue Proteins/biosynthesis Nestin Neurons/drug effects,metabolism,pathology Oxidopamine Parkinsonian Disorders/chemically induced,drug therapy,pathology Rats Rats, Sprague-Dawley Stem Cells/drug effects,pathology Trans-Activators/metabolism Transforming Growth Factor alpha/administration & dosage Tyrosine 3-Monooxygenase/biosynthesis beta Catenin
Chemicals
Ctnnb1 protein, rat Cytoskeletal Proteins Intermediate Filament Proteins Nerve Tissue Proteins Nes protein, rat Nestin Trans-Activators Transforming Growth Factor alpha beta Catenin Oxidopamine Tyrosine 3-Monooxygenase Bromodeoxyuridine Dopamine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Cooper Oliver
Harvard University and McLean Hospital, National Institute of Neurological Disorders and Stroke Udall Parkinson's Disease Research Center of Excellence, Belmont, Massachusetts 02478, USA.
Isacson Ole
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2344-04.2004
Published
2004-10-13
Pages
8924-31
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC2613225
Subset
IM
Grants
NINDS NIH HHS · P50 NS039793 · United States
NINDS NIH HHS · P50 NS039793-05 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.2344-04.2004 PMC Full Text View journal details
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