In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain

James Fallon, Steve Reid, Richard Kinyamu, Isaac Opole, Rebecca Opole, Janie Baratta, Murray Korc, Tiffany L. Endo, Alexander Duong, Gemi Nguyen, Masoud Karkehabadhi, Daniel Twardzik, Sandra Loughlin

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364 Scopus citations

Abstract

The development of an in vivo procedure for the induction of massive proliferation, directed migration, and neurodifferentiation (PMD) in the damaged adult central nervous system would hold promise for the treatment of human neurodegenerative disorders such as Parkinson's disease. We investigated the in vivo induction of PMD in the forebrain of the adult rat by using a combination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic neurons and infusions of transforming growth factor α (TGFα) into forebrain structures. Only in animals with both lesion and infusion of TGFα was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed toward the region of the TGFα infusion site. Subsequently, increasing numbers of differentiated neurons were observed in the striatum. In behavioral experiments, there was a significant reduction of apomorphine-induced rotations in animals receiving the TGFα infusions. These results show that the brain contains stem cells capable of PMD in response to an exogenously administered growth factor. This finding has significant implications with respect to the development of treatments for both acute neural trauma and neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)14686-14691
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number26
DOIs
StatePublished - Dec 19 2000

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    Fallon, J., Reid, S., Kinyamu, R., Opole, I., Opole, R., Baratta, J., Korc, M., Endo, T. L., Duong, A., Nguyen, G., Karkehabadhi, M., Twardzik, D., & Loughlin, S. (2000). In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proceedings of the National Academy of Sciences of the United States of America, 97(26), 14686-14691. https://doi.org/10.1073/pnas.97.26.14686