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

The development of an in vivo procedure for the induction of massive prolif eration, 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 th e in vivo induction of PMD in the forebrain of the adult rat by using a com bination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic n eurons and infusions of transforming growth factor alpha (TGF alpha) into f orebrain structures. Only in animals with both lesion and infusion of TGF a lpha was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed towar d the region of the TGF alpha infusion site. Subsequently, increasing numbe rs of differentiated neurons were observed in the striatum. In behavioral e xperiments, there was a significant reduction of apomorphine-induced rotati ons in animals receiving the TGF alpha infusions. These results show that t he brain contains stem cells capable of PMD in response to an exogenously a dministered growth factor. This finding has significant implications with r espect to the development of treatments for both acute neural trauma and ne urodegenerative diseases.