Fernandez M, Giuliani A, Giardino L, Calza L (2002) In vivo strategies for stem cells regulation in the adult brain: A chance for cholinergic neurons. Neuroscience 2002 Abstracts 483.14. Society for Neuroscience, Orlando, FL.
Summary: Degenerative diseases represent a severe problem in view of very limited repair capability of nervous system. In order to use stem cells in the adult CNS for repair purpose, we are exploring the possibility to influence, in vivo, proliferation, migration and phenotype lineage of stem cells in adult brain using a growth factor, hormone and cytokine cocktail. In this study we used substances appropriate for in vitro cholinergic differentiation in animals lesioned with icv administration of the cholinergic neurons immunotoxin 195IgG-saporine (3microg/4,5microl). Four months after lesion, no ChAT-positive neurons were found in the basal forebrain, acetylcolinesterase-reactive fibres and ChAT activity in the cerebral cortex and hippocampus dramatically decrease, and animals are severely impaired in water maze learning task. An Alzet osmotic Minipump for chronic release (over 14 days) of the mitogen EGF (360ng/days) was then implanted and connected to a icv catheter. This treatment increases proliferation rate in SVZ in lesioned and unlesioned animals as indicated by the widespread distribution of BrDU-positive nuclei in the forebrain. Rats were then treated with retinoic acid (2.25 mg/day, orally). This treatment reduces Ki67 protein in the SVZ in lesioned rats, and this could indicate a progression toward differentiation. TrkA-positive innervation also increase in the basal forebrain of EGF+retinoic acid treated rats and ChAT activity is lightly, but significantly raises by combined EGF + retinoid acid treatment in the hippocampus.
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