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Abnormal activation of astrocytes contributes to some behavior deficits. However, mechanisms underlying the effects remain unclear. Here, we studied the activation of A1 astrocytes and their contribution to murine behavior deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A1 astrocytes were induced by treatment with lipopolysaccharide (LPS) in vitro. The functional phenotype of astrocytes was determined by quantitative RT-PCR, ELISA, and immunohistochemistry. To assess the role of A1 astrocytes in vivo, mice were injected intraperitoneally with LPS. Then, murine behaviors were tested, and the hippocampus and cortex were analyzed by quantitative RT-PCR, ELISA, and immunohistochemistry. The function of IL-10 and fluorocitrate on A1 astrocyte activation was also examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results show that astrocytes isolated from B6.129S6-Il10<jats:sup>tm1Flv<\/jats:sup>\/J homozygotes (IL-10<jats:sup>tm1\/tm1<\/jats:sup>) were prone to characteristics of A1 reactive astrocytes. Compared with their wild-type counterparts, IL-10<jats:sup>tm1\/tm1<\/jats:sup>astrocytes exhibited higher expression of glial fibrillary acidic protein (GFAP). Whether or not they were stimulated with LPS, IL-10<jats:sup>tm1\/tm1<\/jats:sup>astrocytes exhibited enhanced expression of A1-specific transcripts and proinflammatory factors IL-1\u03b2, IL-6, and TNF\u03b1. In addition, IL-10<jats:sup>tm1\/tm1<\/jats:sup>astrocytes demonstrated hyperphosphorylation of STAT3. Moreover, astrocytes from IL-10<jats:sup>tm1\/tm1<\/jats:sup>mice showed attenuated phagocytic ability and were neurotoxic. IL-10<jats:sup>tm1\/tm1<\/jats:sup>mice demonstrated increased immobility time in the forced swim test and defective learning and memory behavior in the Morris water maze test. Moreover, enhanced neuroinflammation was found in the hippocampus and cortex of IL-10<jats:sup>tm1\/tm1<\/jats:sup>mice, accompanying with more GFAP-positive astrocytes and severe neuron loss in the hippocampus. Pretreatment IL-10<jats:sup>tm1\/tm1<\/jats:sup>mice with IL-10 or fluorocitrate decreased the expression of proinflammatory factors and A1-specific transcripts in the hippocampus and cortex, and then alleviated LPS-induced depressive-like behavior.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that astrocytes isolated from B6.129S6-Il10<jats:sup>tm1Flv<\/jats:sup>\/J homozygotes are prone to A1 phenotype and contribute to the depression-like behavior and memory deficits. Inhibiting A1 astrocyte activation may be an attractive therapeutic strategy in some neurodegenerative diseases.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-020-01871-9","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T13:41:57Z","timestamp":1593610917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["A1 astrocytes contribute to murine depression-like behavior and cognitive dysfunction, which can be alleviated by IL-10 or fluorocitrate treatment"],"prefix":"10.1186","volume":"17","author":[{"given":"He-Yang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youdi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Ming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Nv","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1401-9653","authenticated-orcid":false,"given":"Xiao-Xia","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"issue":"7","key":"1871_CR1","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/nn.4043","volume":"18","author":"BS Khakh","year":"2015","unstructured":"Khakh BS, Sofroniew MV. 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