Lack of neurogenesis in the adult rat cerebellum after Purkinje cell degeneration and growth factor infusion.
Although constitutive neurogenesis exclusively occurs in restricted regions of the adult mammalian brain, resident progenitors can be isolated from many different CNS sites, and neuronal neogeneration can be stimulated in vivo by injury or infusion of growth factors. To ask whether latent compensatory mechanisms, which may be exploited to promote repair processes, are present throughout the CNS, we examined the neurogenic potentialities of the adult rat cerebellum in normal conditions, following injury, and after infusion of growth factors. Degeneration of Purkinje cells was induced by intracerebroventricular administration of the toxin saporin, conjugated to anti-p75 antibodies. In addition, epidermal growth factor and basic fibroblast growth factor, or FGF8, were infused for 2 weeks to either intact or injured animals. In all conditions, proliferating cells were identified from bromodeoxyuridine (BrdU) incorporation. In the unmanipulated cerebellum there were rare dividing cells, mainly represented by NG2-positive presumptive oligodendrocyte precursors. Mitotic activity was strongly enhanced in cortical areas with Purkinje cell degeneration, being mostly sustained by microglia, plus minor fractions of NG2-expressing cells, astrocytes and oligodendrocytes. In contrast, growth factor infusion had a weak effect on both intact and injured cerebella. In all experimental conditions, we never found any BrdU-positive cells coexpressing distinctive markers for immature or differentiated cerebellar neurons. Therefore, although some progenitor cells reside in the adult cerebellum, the local environment, either intact or injured, does not provide efficient cues to direct their differentiation towards neuronal phenotypes. In addition, neurogenic potentialities cannot be induced or boosted by the application of growth factors which are effective in other CNS regions.
Grimaldi
Piercesare
P
Rita Levi Montalcini Centre for Brain Repair, Department of Neuroscience, University of Turin, Corso Raffaello 30, I-10125 Turin, Italy. piercesare.grimaldi@unito.it
Rossi
Ferdinando
F
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000293:injuries; D009410:Nerve Degeneration / Q000139:chemically induced; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D011689:Purkinje Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000633:toxicity; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
D011993:Recombinant Fusion Proteins; D020932:Nerve Growth Factor