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Partial depletion and repopulation of microglia have different effects in the acute MPTP mouse model of Parkinson's disease.
Li, Qing; Shen, Chenye; Liu, Zhaolin; Ma, Yuanyuan; Wang, Jinghui; Dong, Hongtian; Zhang, Xiaoshuang; Wang, Zishan; Yu, Mei; Ci, Lei; Sun, Ruilin; Shen, Ruling; Fei, Jian; Huang, Fang.
Afiliación
  • Li Q; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Shen C; Shanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC, Shanghai, China.
  • Liu Z; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Ma Y; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Wang J; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Dong H; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Zhang X; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Wang Z; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Yu M; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Ci L; Department of Translational Neuroscience, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Jing' an District Centre Hospital of Shanghai Institutes of Brain Science, Fudan University, Shanghai, China.
  • Sun R; Shanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC, Shanghai, China.
  • Shen R; Shanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC, Shanghai, China.
  • Fei J; Joint Laboratory for Technology of Model Organism, Shanghai Laboratory Animal Research Center and School of Life Science and Technology, Tongji University.
  • Huang F; Shanghai Laboratory Animal Research Center, Shanghai, China.
Cell Prolif ; 54(8): e13094, 2021 Aug.
Article en En | MEDLINE | ID: mdl-34312932
OBJECTIVES: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive and selective degeneration of dopaminergic neurons. Microglial activation and neuroinflammation are associated with the pathogenesis of PD. However, the relationship between microglial activation and PD pathology remains to be explored. MATERIALS AND METHODS: An acute regimen of MPTP was administered to adult C57BL/6J mice with normal, much reduced or repopulated microglial population. Damages of the dopaminergic system were comprehensively assessed. Inflammation-related factors were assessed by quantitative PCR and Multiplex immunoassay. Behavioural tests were carried out to evaluate the motor deficits in MPTP-challenged mice. RESULTS: The receptor for colony-stimulating factor 1 inhibitor PLX3397 could effectively deplete microglia in the nigrostriatal pathway of mice via feeding a PLX3397-formulated diet for 21 days. Microglial depletion downregulated both pro-inflammatory and anti-inflammatory molecule expression at baseline and after MPTP administration. At 1d post-MPTP injection, dopaminergic neurons showed a significant reduction in PLX3397-fed mice, but not in control diet (CD)-fed mice. However, partial microglial depletion in mice exerted little effect on MPTP-induced dopaminergic injuries compared with CD mice at later time points. Interestingly, microglial repopulation brought about apparent resistance to MPTP intoxication. CONCLUSIONS: Microglia can inhibit PD development at a very early stage; partial microglial depletion has little effect in terms of the whole process of the disease; and microglial replenishment elicits neuroprotection in PD mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Intoxicación por MPTP Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Prolif Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Intoxicación por MPTP Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Prolif Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido