Enhanced de novo neurogenesis and dopaminergic neurogenesis in the substantia nigra of MPTP-induced Parkinson's disease-like mice

¹ Department of Anatomy and Cell Biology, University of North Dakota School of Medicine, Grand Forks, North Dakota

^* To whom correspondence should be addressed. E-mail: rliu{at}medicine.nodak.edu.

	Abstract

Research reports on de novo neurogenesis, particularly dopaminergic (DA) neurogenesis in the adult mammalian substantia nigra (SN) remain very controversial. For this reason, we utilized the nestin second-intron enhancer controlled LacZ reporter (pNes-LacZ) transgenic mouse model coupled with MPTP lesion system to investigate whether there are neurogenesis and DA neurogenesis in the SN of the adult normal and Parkinson's disease (PD)-like mice. First, we demonstrated the presence of neural progenitor cells (NPCs), basal levels of neurogenesis, and DA neurogenesis in the normal adult mouse SN. Second, we showed there is not only a significant increase in the number of NPCs, but also a dramatic increase of neurogenesis from the NPCs in the SN and the midline region adjacent to the SN of the PD-like mice, compared with that of normal controls. More importantly, we also demonstrated there is an increase of DA neurogenesis in the SN of the MPTP lesioned mice. Third, we showed that the increased DA neurogenesis in the MPTP lesioned mice was derived from the NPCs and BrdU positive cells, suggesting multiple stem cell lineages may contribute to the enhanced neurogenesis in the adult SN. Taken together, these results establish that there are basal levels, albeit low, and increased levels of de novo neurogenesis and DA neurogenesis in the SN of the adult normal and PD-like mice respectively. The increased NPCs in the MPTP lesioned mice further suggest that experimental approaches to promote de novo neurogenesis may provide an effective therapy for PD by functional replacement of degenerated DAs.