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| The DJ-1 gene, originally identified as an oncogene, is a causative gene for a familial form of Parkinson's disease (PD), PARK7. DJ-1 protein was found to play multiple roles in various physiological and pathological processes including cellular transformation, regulating oxidative stress and transcription, as well as cell growth and death. We found previously that DJ-1 was closely associated with the proliferation and differentiation of cultured neuronal stem cells. In this study, we further investigated other functions of DJ-1, in an attempt to determine how adult neurogenesis was affected in the subgranular zones (SGZ), the subventricular zone (SVZ) and olfactory bulb (OB), the brain areas closely related to early non-motor symptoms of PD, using an MPTP-induced mouse PD model. The results demonstrated that the number of BrdU+ cells in SGZ for both MPTP-treated and saline control groups were not significantly different. However, increased migration of BrdU+ cells into the olfactory glomerulus layer of OB was observed 14 days after MPTP injection, suggesting a compensatory mechanism might exist to restore neuronal loss. Specifically, we found that DJ-1 was translocated into the nuclei of the BrdU+ cells in SGZ and SVZ, but not in OB. A plausible explanation is that the nuclear translocation of DJ-1 mainly occurs in the early stages of adult NSCs proliferation in vivo. However, within the BrdU- cells in the olfactory glomerulus layer of OB, DJ-1 was concentrated into nuclei. These results indicated that the nuclear translocation of DJ-1 might be involved in maintaining the olfactory function of mature olfactory neurons. The research presented here thus provided evidence on using DJ-1 as a tool and biomarker for PD early diagnosis, stratification and possibly therapeutic treatments. |
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| Keywords:Pharmacology; Parkinson's disease; Neuronal stem cell; Neurogenesis; DJ-1; Nuclear translocation |
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