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Contemporary discoveries demonstrate a local inflammatory response in peripheral organs can trigger inflammation in the brain, particularly the hippocampus, mediated through the NLRP3 inflammasome. Critically, central inflammation causes depressive behavior. Since bladder outlet obstruction (BOO) evokes a local inflammatory response in the bladder, we hypothesize it will induce NLRP3\u2010dependent inflammation in the hippocampus and depressive behavior.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>There were four groups of rats: control, sham, BOO, or BOO\u2009+\u2009glyburide (an NLRP3 inhibitor). BOO was created by urethral ligation over a 1\u2009mm catheter. Sham was tied loosely. Glyburide was provided by slow\u2010release pellet (subcutaneous 50\u2009mg, 21 day, replaced as needed). Rats were analyzed 12 weeks post\u2010op for: hippocampal inflammation, microglial density, neurogenesis, and depression symptoms (open field and sucrose preference).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BOO elicited hippocampal inflammation, accompanied by an increase in activated microglia (22%) and a decrease in neurogenesis (35%), which was blocked by glyburide. In addition, BOO rats displayed anxiety (57% decrease in exploratory behavior in the open field assay) and anhedonia (21% decrease in sucrose preference), two symptoms of depression. Like inflammation, these symptoms were diminished by glyburide to levels not statistically significantly different from controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BOO, a bladder\u2010localized event, stimulates NLRP3\u2010dependent inflammation in the rat hippocampus after 12 weeks and this inflammation causes depressive behavior. This is the first mechanistic explanation of the link between BOO and depression and provides evidence for a distinct bladder\u2010brain axis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24448","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T05:17:26Z","timestamp":1593494246000},"page":"1700-1707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A possible mechanism underlying mood disorders associated with LUTS: Chronic bladder outlet obstruction causes NLRP3\u2010dependent inflammation in the hippocampus and depressive behavior in rats"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3776-3653","authenticated-orcid":false,"suffix":"Jr.","given":"Francis M.","family":"Hughes","sequence":"first","affiliation":[{"name":"Division of Urology, Department of Surgery Duke University Medical Center Durham North Carolina"},{"name":"Department of Bioengineering Clemson University Clemson South Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-1209","authenticated-orcid":false,"given":"Nathan A.","family":"Hirshman","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Duke University Medical Center Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-0374","authenticated-orcid":false,"given":"Hamza A.","family":"Malick","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Duke University Medical Center Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon W.","family":"White","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Duke University Medical Center Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4645-2478","authenticated-orcid":false,"given":"Huixia","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Duke University Medical Center Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-6101","authenticated-orcid":false,"given":"Shelby N.","family":"Harper","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Duke University Medical Center Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-2047","authenticated-orcid":false,"given":"J. Todd","family":"Purves","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Duke University Medical Center Durham North Carolina"},{"name":"Department of Pediatrics Duke University Medical Center Durham North Carolina"},{"name":"Department of Bioengineering Clemson University Clemson South Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2009.08371.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.12.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23421"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-014-0054-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2018-000835"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2018.02.890"},{"key":"e_1_2_8_8_1","first-page":"51","article-title":"Relationship between depression and lower urinary tract symptoms secondary to benign prostatic hyperplasia","volume":"17","author":"Dunphy C","year":"2015","journal-title":"Rev Urol"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24184"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.12.068"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00400.2018"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23419"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2010.01.069"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00408.2019"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.03.002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)00815-3"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134476"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.06.038"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6871089"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2011.07.001"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076017"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.06.018"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.2015.13.3.269"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2003.10.016"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.2000.00839.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903124"}],"container-title":["Neurourology and Urodynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fnau.24448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.24448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/nau.24448","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.24448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T20:27:14Z","timestamp":1693945634000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/nau.24448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,29]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/nau.24448"],"URL":"https:\/\/doi.org\/10.1002\/nau.24448","archive":["Portico"],"relation":{},"ISSN":["0733-2467","1520-6777"],"issn-type":[{"value":"0733-2467","type":"print"},{"value":"1520-6777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,29]]},"assertion":[{"value":"2020-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}