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Reduced VMAT2 expression exacerbates the hyposmia in the MPTP model of Parkinson's disease
Kai Ma1, Chao Han2, Guoxin Zhang1
1Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Abstract:
Hyposmia occurs during the prodromal phase of Parkinson's disease (PD), while the underlying mechanisms remain unclear. Discussed are altered dopamine content and impairment of neurogenesis of olfactory bulbs (OB), which has been suggested to be linked to olfactory dysfunction. Given that mouse with reduced vesicular monoamine transporter 2 (VMAT2) expression is now deemed as a relatively new PD animal model simulating motor and nonmotor symptoms, it may provide a new insight into investigating the mechanisms of hyposmia in the context of PD. In this study, we examined the effect of subacute administration of MPTP on mice with a reduced expression of VMAT2, focusing on the histopathological and biochemical alterations, specifically, TH expression level, dopamine content as well as neurogenesis in OB. Interestingly, mice with a reduced VMAT2 expression displayed more obvious olfactory impairment in response to MPTP administration accompanied by markedly decreased dopaminergic interneurons in OB. Furthermore, neurogenesis in OB was also further impaired after MPTP due to reduced VMAT2 expression. We therefore demonstrated that reduced expression of VMAT2 contributed to the impairment of hyposmia, pathologically, the degeneration of extranigral systems and reduced neurogenesis might be the underlying mechanisms.
Insights
Reduced vesicular monoamine transporter 2 (VMAT2) expression exacerbates olfactory impairment in Parkinson's disease models. This impairment is linked to decreased dopaminergic neurons and impaired neurogenesis in the olfactory bulb.
Area of Science:
- Neuroscience
- Pathology
Background:
- Hyposmia (impaired sense of smell) is an early symptom of Parkinson's disease (PD).
- The mechanisms behind PD-related hyposmia, including altered dopamine and neurogenesis in the olfactory bulb (OB), are not fully understood.
- Mice with reduced vesicular monoamine transporter 2 (VMAT2) expression serve as a model for PD, exhibiting motor and non-motor symptoms.
Purpose of the Study:
- To investigate the role of reduced VMAT2 expression in MPTP-induced olfactory dysfunction in a mouse model.
- To examine the histopathological and biochemical changes in the olfactory bulb.
Main Methods:
- Subacute administration of MPTP to mice with reduced VMAT2 expression.
- Assessment of tyrosine hydroxylase (TH) expression, dopamine content, and neurogenesis in the olfactory bulb.
Main Results:
- Mice with reduced VMAT2 showed exacerbated olfactory impairment after MPTP exposure.
- MPTP administration led to a significant decrease in dopaminergic interneurons in the OB of VMAT2-reduced mice.
- Neurogenesis in the OB was further impaired in these mice.
Conclusions:
- Reduced VMAT2 expression contributes to hyposmia in Parkinson's disease.
- Degeneration of extranigral systems and impaired neurogenesis in the OB are potential underlying mechanisms.