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Alpha7 nicotinic acetylcholine receptors (\u03b17nAChRs) regulate the cholinergic anti-inflammatory pathway, but the role of cholinergic signaling and \u03b17nAChR in chronic stress has not yet been examined.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this study, we used a well-documented model of depression in which mice were exposed to 6\u00a0h of restraint stress for 21 consecutive days. Components of cholinergic signaling and TLR4 signaling were analyzed in the hippocampus. The main targets of neuroinflammation and neuronal damage were also evaluated after a series of tests for depression-like behavior.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Chronic restraint stress (CRS) induced alterations in components of central cholinergic signaling in hippocampus, including increases in choline acetyltransferase protein expression and decreases in nuclear STAT3 signaling. CRS also increased TLR4 signaling activity, interleukin-1\u03b2, and tumor necrosis factor-\u03b1 expression, microglial activation, and neuronal morphologic changes. Cholinergic stimulation with the \u03b17nAChR agonist DMXBA significantly alleviated CRS-induced depressive-like behavior, neuroinflammation, and neuronal damage, but these effects were abolished by the selective \u03b17nAChR antagonist \u03b1-bungarotoxin. Furthermore, activation of \u03b17nAChRs restored the central cholinergic signaling function, inhibited TLR4-mediated inflammatory signaling and microglial activity, and increased the number of regulatory T cells in the hippocampus.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These findings provide evidence that \u03b17nAChR activation mitigates CRS-induced neuroinflammation and cell death, suggesting that \u03b17nAChRs could be a new therapeutic target for the prevention and treatment of depression.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-017-1007-2","type":"journal-article","created":{"date-parts":[[2017,12,2]],"date-time":"2017-12-02T07:40:20Z","timestamp":1512200420000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates depressive-like behavior in a mouse model of chronic stress"],"prefix":"10.1186","volume":"14","author":[{"given":"Dan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linna","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopei","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianjun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,2]]},"reference":[{"key":"1007_CR1","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/j.neubiorev.2009.05.004","volume":"33","author":"T Buynitsky","year":"2009","unstructured":"Buynitsky T, Mostofsky DI. 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