{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:08:50Z","timestamp":1787501330556,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T00:00:00Z","timestamp":1329091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microglia are intrinsic immune cells in the brain. In response to neurodegenerative events, excessively activated microglia change their shapes and release various cytokines leading to the pathogenesis of central nervous system (CNS) disease. Because the intracellular mechanisms of this process are still unclear, we have evaluated the functional roles of transient receptor potential vanilloid 4 (TRPV4) channel expressed in the microglia. Robust microglial activation after an injection of lipopolysaccharide (LPS) into the mouse cerebral ventricle was suppressed by concurrent administration of a selective TRPV4 agonist, 4\u03b1\u2010phorbol 12,13\u2010didecanoate (4\u03b1\u2010PDD). When the mechanism was further investigated using cultured rat microglia intrinsically expressing functional TRPV4, release of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and expression of galectin\u20103 were both increased by LPS. These increases were significantly suppressed by cotreatment with 4\u03b1\u2010PDD, and the inhibitory effects of 4\u03b1\u2010PDD were abolished by knockdown of TRPV4 or TRPV4 antagonists. The amplitude of voltage\u2010dependent K\n                    <jats:sup>+<\/jats:sup>\n                    current, which is augmented during microglial activation, was also suppressed by 4\u03b1\u2010PDD treatment. Opening of TRPV4 channels with 4\u03b1\u2010PDD induced membrane depolarization mainly by increasing Na\n                    <jats:sup>+<\/jats:sup>\n                    influx. In addition, mimicking depolarization with a high\u2010K\n                    <jats:sup>+<\/jats:sup>\n                    solution suppressed LPS\u2010induced TNF\u2010\u03b1 release and galectin\u20103 upregulation. Both depolarizing treatments with 4\u03b1\u2010PDD and high\u2010K\n                    <jats:sup>+<\/jats:sup>\n                    solution decreased store\u2010operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx caused by thapsigargin. These results suggest that depolarization in response to opening of the TRPV4 channel attenuates the driving force for extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and suppresses microglial activation. \u00a9 2012 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/glia.22306","type":"journal-article","created":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T14:37:31Z","timestamp":1329143851000},"page":"761-770","source":"Crossref","is-referenced-by-count":79,"title":["Stimulation of transient receptor potential vanilloid 4 channel suppresses abnormal activation of microglia induced by lipopolysaccharide"],"prefix":"10.1002","volume":"60","author":[{"given":"Masakazu","family":"Konno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Shirakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Iida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Sakimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikkei","family":"Matsutani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Kageyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Shibasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.145151"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.06.039"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70062357.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00029-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20476"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.12.003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20412"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00398-O"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1251-05.2005"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00469.2009"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302517200"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0622-0"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1997"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14294"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701732"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304487200"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3593-06.2007"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2010"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4322"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.12.035"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00331.2003"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00719-5"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02120.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.020206"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.10075SC"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00365.2003"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1136(200010)32:1<51::AID-GLIA50>3.0.CO;2-4"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4284-06.2007"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1890-10.2010"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10154"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000039345.00481.1D"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199801)22:1<1::AID-GLIA1>3.0.CO;2-C"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0303329101"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20000815)61:4<430::AID-JNR9>3.0.CO;2-3"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200062200"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01807"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002725"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.22306","content-type":"unspecified","content-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