Effects of 6-hydroxydopamine on the Adult Neurogenesis of Dopaminergic Neurons in the Mouse Midbrain

Abstract

Recently, restricted progenitor cells have been identified in the substantia nigra (SN) of the rat and mouse, raising a hope that resident stem/progenitor cells may be useful for the therapy of Parkinson's disease. However, it is controversial whether dopamine (DA) neurons can be spontaneously or injury-dependently generated from the endogenous stem cells in the adult brain. Here, we explored the neurogenesis in C57Bl/6 adult mice under the normal and neurotoxin-injured conditions. To monitor adult neurogenesis, we injected 5-bromodeoxyuridine (BrdU) 2 weeks after striatal injection of neurotoxin 6-hydroxydopamine (6-OHDA), and sacrificed the animals 6 weeks after 6-OHDA injection. Whereas the number of BrdU-labeled cells was slightly increased in ipsilateral side than contralateral side of the midbrain, none of BrdUlabeled cells, however, exhibited neuronal markers, NeuN or DCX. Instead, BrdUlabeled cells expressed glial markers such as GFAP (astrocyte), Olig2 (oligodendrocyte) and Iba-1 (microglia). Especially, larger portion of BrdU-labeled cells in the ipsilateral side exhibited microglial marker, indicating that increased cell production in response to the 6-OHDA injection is not related to the adult neurogenesis.

Adult Neurogenesis in the Central and Peripheral Nervous Systems

“…Thus, an imbalance in the self-renewal process may directly cause PD. However, we and others failed to replicate this experiment in mice and rats, and further evaluations are required [ 51 , 52 ]. More recently, Perera et al's report [ 53 ] demonstrated that the effect of antidepressant fluoxetine is mediated by increased neurogenesis, thus promoting the idea that depression may be caused by reduced adult neurogenesis.…”