Related Experiment Video
Updated: Aug 11, 2026
Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease
Published on: June 17, 2013
Transiently impaired neurogenesis in MPTP mouse model of Parkinson's disease
Xi Jun He1, Hiroyuki Nakayama2
1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin 150001, People's Republic of China; Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Abstract:
It is still being debated whether neurogenesis in the subventricular zone (SVZ) is enhanced in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injury in the adult mouse brain. Our previous studies provided evidence that MPTP induces apoptosis of migrating neuroblasts (neural progenitor cells, A cells) in the SVZ and rostral migratory stream (RMS). We investigated cellular kinetics in the adult SVZ and olfactory bulb (OB) after MPTP damage. Cells were labeled with bromodeoxyuridine (BrdU), and the effects of MPTP on the survival and fate of migrating and residing neuroblasts were evaluated. Two days after BrdU labeling and MPTP treatment, the number of BrdU-positive cells in the SVZ and OB of MPTP-treated mice was significantly lower than in the SVZ and OB of saline controls. Additionally, fewer BrdU-positive cells migrated to the OB of treated mice than to that of saline controls, and the cells that did migrate diffused radially into the granule cell layer (GCL) when observed at 7, 14, and 28 days. In the OB GCL, the differentiation of BrdU-positive cells into mature neurons significantly attenuated 14 and 28 days after MPTP injury. Moreover, the impaired neurogenesis was followed by a recovery of A cells in the SVZ and OB, suggesting activation of the self-repair process as a result of MPTP-induced depletion of BrdU-positive cells. Our findings clarify the kinetics underlying neurogenesis in MPTP-treated mice and may contribute to the development of an animal model of Parkinson's disease, and the demonstration of cellular kinetics in SVZ may also provide a new insight into assessing neurogenesis in MPTP-treated mouse.
Insights
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injury reduces neurogenesis in adult mice by decreasing neuroblast survival and migration. However, the brain shows signs of self-repair after MPTP damage.
Area of Science:
- Neuroscience
- Cell Biology
- Neurodegenerative Diseases
Background:
- The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on adult neurogenesis remains debated.
- Previous studies suggest MPTP induces apoptosis in migrating neuroblasts within the subventricular zone (SVZ) and rostral migratory stream (RMS).
Purpose of the Study:
- To investigate the cellular kinetics of neurogenesis in the SVZ and olfactory bulb (OB) following MPTP injury in adult mice.
- To evaluate the impact of MPTP on the survival, migration, and differentiation of neuroblasts.
Main Methods:
- Adult mice were treated with MPTP or saline and labeled with bromodeoxyuridine (BrdU).
- Cellular kinetics, including cell survival, migration to the OB, and differentiation into mature neurons, were assessed at various time points (2, 7, 14, and 28 days post-treatment).
Main Results:
- MPTP treatment significantly reduced the number of BrdU-positive cells in the SVZ and OB compared to controls.
- Reduced migration of BrdU-positive cells to the OB was observed, with surviving cells showing radial diffusion in the granule cell layer (GCL).
- Differentiation of BrdU-positive cells into mature neurons in the OB GCL was significantly attenuated 14 and 28 days after MPTP injury.
Conclusions:
- MPTP injury impairs neurogenesis by affecting neuroblast survival and migration, leading to reduced neuronal differentiation.
- The observed recovery of neuroblasts suggests an endogenous self-repair mechanism activated by MPTP-induced cell depletion.
- These findings provide insights into neurogenesis kinetics in MPTP-treated mice, potentially aiding in the development of Parkinson's disease models and assessment of neurogenesis.
Related Concept Videos
01:24Parkinson Disease l: Introduction
01:24Parkinson Disease ll: Pathophysiology