{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:04:18Z","timestamp":1792843458980,"version":"4.5.0"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Transcutaneous auricular vagus nerve stimulation (taVNS) is a vital neuromodulation for the treatment of depression, but its antidepressant molecular mechanism is unclear. The \u03b17 nicotinic acetylcholine receptor (\u03b17nAchR) is a key mediator of the vagus nerve that mediates its anti\u2010inflammatory efficacy. Here, we investigated whether the antidepressant effect of taVNS in chronic unpredicted mild stress (CUMS)\u2010exposed rats works through the \u03b17nAchR\/JAK2\/STAT3\/NF\u2010\u03baB pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The depression model was established by CUMS for continuous 6\u2009weeks in rats. From the 4th week of the experiment, CUMS\u2010exposed rats were subjected to taVNS for 3\u2009weeks. To clarify the role of \u03b17nAchR in the antidepressant effect of taVNS, we used \u03b17nAchR<jats:sup>\u2212\/\u2212<\/jats:sup> gene knockout rats. The sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were used to evaluate depression\u2010like behaviors of rats. Immunofluorescent staining was used to observe the morphology of microglia in the hypothalamus. Western blot was used to examine the protein expression of \u03b17nAchR, p\u2010JAK2, p\u2010STAT3, IL\u20101\u03b2, NF\u2010\u03baB p65, and p\u2010NF\u2010\u03baB p65 in the hypothalamus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Depression\u2010like behaviors in CUMS\u2010exposed rats were manifested by decreased SPT ratio, increased FST immobility time, decreased total distance, vertical movement score, and activity time of OFT. Hypothalamic neuroinflammation in CUMS\u2010exposed rats was manifested by an amoebic\u2010like activated state of microglia, downregulated expression of \u03b17nAchR, p\u2010JAK2, p\u2010STAT3, and upregulated expression of NF\u2010\u03baB p65, p\u2010NF\u2010\u03baB p65, and IL\u20101\u03b2. TaVNS could significantly reverse the above\u2010mentioned phenomena, but had a poor improvement effect for CUMS\u2010exposed \u03b17nAchR<jats:sup>\u2212\/\u2212<\/jats:sup> rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The hypothalamic \u03b17nAchR\/JAK2\/STAT3\/NF\u2010\u03baB signaling pathway may play an important role in the antidepressant\u2010like behavior of taVNS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14207","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T07:24:53Z","timestamp":1681111493000},"page":"2634-2644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Anti\u2010neuroinflammation effects of transcutaneous auricular vagus nerve stimulation against depression\u2010like behaviors via hypothalamic <scp>\u03b17nAchR<\/scp>\/<scp>JAK2<\/scp>\/<scp>STAT3<\/scp>\/<scp>NF\u2010\u03baB<\/scp> pathway in rats exposed to chronic unpredictable mild stress"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7498-8136","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-9261","authenticated-orcid":false,"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"},{"name":"Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5070-0038","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7288-2319","authenticated-orcid":false,"given":"Peijing","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences  Beijing 100700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Depression and Other Common Mental Disorders: Global Health Estimates","author":"World Health Organization","year":"2017"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30385-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31948-2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2007.01.011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001805"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3295"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1475-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2014.11.018"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-020-00619-y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ner.12541"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/786839"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000013845"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.02.031"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.03.025"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/627023"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8885729"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01321"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.07.004"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.03.018"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13022219"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108053"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-25572"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2018-0027"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050456"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-019-00807-3"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02341-6"},{"issue":"5","key":"e_1_2_11_28_1","first-page":"4195","article-title":"Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta\u2010analysis","volume":"55","author":"K\u00f6hler CA","year":"2018","journal-title":"Mol Neurobiol"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-320912"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00187257"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00680"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/789674"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2018.05.018"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.150052"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.06.003"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135031"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.907628"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2017.03.002"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2017.00015"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibror.2018.11.008"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-019-00447-9"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S141033"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2020.03.005"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.01.021"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.316"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0516-y"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113191"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2004.02347.x"},{"issue":"3","key":"e_1_2_11_49_1","first-page":"971","article-title":"Activation of the \u03b17 nicotinic receptor promotes lipopolysaccharide\u2010induced conversion of M1 microglia to M2","volume":"9","author":"Zhang Q","year":"2017","journal-title":"Am J Transl Res"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1007-2"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370215619707"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.08.031"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.043"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00197"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1159\/000504444"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112066"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12983"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13805"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4112"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X211019827"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X211021313"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X21999553"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.05.001"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T07:57:45Z","timestamp":1718006265000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.14207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,10]]},"references-count":62,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/cns.14207"],"URL":"https:\/\/doi.org\/10.1111\/cns.14207","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,10]]},"assertion":[{"value":"2022-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}