Partial depletion and repopulation of microglia have different effects in the acute MPTP mouse model of Parkinson's disease
| Autor: | Ruilin Sun, Ruling Shen, Jian Fei, Zishan Wang, Chenye Shen, Lei Ci, Mei Yu, Zhaolin Liu, Jinghui Wang, Xiaoshuang Zhang, Fang Huang, Yuanyuan Ma, Hongtian Dong, Qing X. Li |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Parkinson's disease Population Nigrostriatal pathway Aminopyridines Pharmacology Neuroprotection nigrostriatal axis chemistry.chemical_compound Mice Medicine Animals Pyrroles Receptors Immunologic education Neuroinflammation education.field_of_study Membrane Glycoproteins Microglia Behavior Animal business.industry MPTP Dopaminergic Neurons Dopaminergic MPTP Poisoning Cell Biology General Medicine Original Articles medicine.disease Mice Inbred C57BL Disease Models Animal microglial depletion medicine.anatomical_structure Neuroprotective Agents chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Cyclooxygenase 2 Cytokines Original Article Inflammation Mediators business microglial repopulation |
| Zdroj: | Cell Proliferation |
| ISSN: | 1365-2184 |
| Popis: | 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. PLX3397 can efficiently eliminate microglia in the nigrostriatal pathway; Microglia are neuroprotective at early time post‐MPTP injection; Microglial depletion has little effect on the progression of PD in mice; Repopulated microglia exhibit a protective effect in MPTP‐induced PD mice.Microglial depletion in the nigrostriatal pathway has little effect on the progression of PD in mice, while repopulated microglia exhibit a protective effect in MPTP mouse models. |
| Databáze: | OpenAIRE |
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