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Microglial activation and neuroinflammation are associated with the pathogenesis of PD. However, the relationship between microglial activation and PD pathology remains to be explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>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\u2010related factors were assessed by quantitative PCR and Multiplex immunoassay. Behavioural tests were carried out to evaluate the motor deficits in MPTP\u2010challenged mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The receptor for colony\u2010stimulating factor 1 inhibitor PLX3397 could effectively deplete microglia in the nigrostriatal pathway of mice via feeding a PLX3397\u2010formulated diet for 21\u00a0days. Microglial depletion downregulated both pro\u2010inflammatory and anti\u2010inflammatory molecule expression at baseline and after MPTP administration. At 1d post\u2010MPTP injection, dopaminergic neurons showed a significant reduction in PLX3397\u2010fed mice, but not in control diet (CD)\u2010fed mice. However, partial microglial depletion in mice exerted little effect on MPTP\u2010induced dopaminergic injuries compared with CD mice at later time points. Interestingly, microglial repopulation brought about apparent resistance to MPTP intoxication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13094","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T01:51:17Z","timestamp":1627350677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Partial depletion and repopulation of microglia have different effects in the acute MPTP mouse model of Parkinson\u2019s disease"],"prefix":"10.1111","volume":"54","author":[{"given":"Qing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Translational Neuroscience State Key Laboratory of 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