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Understanding the phenotype switch of microgliosis in PD could help to identify the molecular mechanism which could attenuate or delay the progressive decline in motor function. KCa3.1 has been reported to regulate the \u201cpro-inflammatory\u201d phenotype switch of microglia in neurodegenerative pathological conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We here investigated the effects of gene deletion or pharmacological blockade of KCa3.1 activity in wild-type or KCa3.1<jats:sup>\u2212\/\u2212<\/jats:sup>mice after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mouse model of PD. MPTP-induced PD mouse model was subjected to the rotarod test to evaluate the locomotor ability. Glia activation and neuron loss were measured by immunostaining. Fluo-4 AM was used to measure cytosolic Ca<jats:sup>2+<\/jats:sup>level in 1-methyl-4-phenylpyridinium (MPP<jats:sup>+<\/jats:sup>)-induced microgliosis in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report that treatment of MPTP-induced PD mouse model with gene deletion or pharmacological blockade of KCa3.1 with senicapoc improves the locomotor ability and the tyrosine hydroxylase (TH)-positive neuron number and attenuates the microgliosis and neuroinflammation in the substantia nigra pars compacta (SNpc). KCa3.1 involves in store-operated Ca<jats:sup>2+<\/jats:sup>entry-induced Ca<jats:sup>2+<\/jats:sup>overload and endoplasmic reticulum stress via the protein kinase B (AKT) signaling pathway during microgliosis. Gene deletion or blockade of KCa3.1 restored AKT\/mammalian target of rapamycin (mTOR) signaling both in vivo and in vitro<jats:italic>.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these results demonstrate a key role for KCa3.1 in driving a pro-inflammatory microglia phenotype in PD.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-019-1682-2","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T08:02:37Z","timestamp":1577347357000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The potassium channel KCa3.1 represents a valid pharmacological target for microgliosis-induced neuronal impairment in a mouse model of Parkinson\u2019s disease"],"prefix":"10.1186","volume":"16","author":[{"given":"Jia","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangfang","family":"Dou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"issue":"3","key":"1682_CR1","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1093\/hmg\/ddt465","volume":"23","author":"MA Nalls","year":"2014","unstructured":"Nalls MA, et al. 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