Beschreibung:
<jats:p>
The development of an
<jats:italic>in vivo</jats:italic>
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
<jats:italic>in
vivo</jats:italic>
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.
</jats:p>