{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:11:59Z","timestamp":1772118719795,"version":"3.50.1"},"reference-count":76,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG058814"],"award-info":[{"award-number":["R01AG058814"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 NS125332\u201001"],"award-info":[{"award-number":["R21 NS125332\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["PP\u20101905\u201033994"],"award-info":[{"award-number":["PP\u20101905\u201033994"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple sclerosis (MS) is a chronic, progressively debilitating demyelinating disease of the central nervous system (CNS). Nearly 80% of MS patients experience lower urinary tract dysfunction early in their diagnosis. This significantly affects the quality of life, and in latter stages of disease is a leading cause of hospitalization. Previously, animal models have shown that inflammatory demyelination in the CNS causes profound bladder dysfunction, but the confounding influence of systemic inflammation limits the potential interpretation of the contribution of CNS demyelination to bladder dysfunction. Since the micturition circuit has myelinated neuronal connections in the cortex, brainstem, and spinal cord, we examined alterations in bladder function in the cuprizone model characterized by demyelinating lesions in the cortex and corpus callosum that are independent of T\u2010cell\u2013mediated autoimmunity. Herein, we report that a 4\u2010week dietary cuprizone treatment in C57Bl\/6J mice induced alterations in voiding behavior with increased micturition frequency and reduced volume voided, similar to human MS bladder dysfunction. Subsequently, recovery from cuprizone treatment restored normal bladder function. Demyelination and remyelination were confirmed by Luxol Fast Blue staining of the corpus callosum. Additionally, we also determined that an 8\u2010week cuprizone treatment, resulting in chronic demyelination lacking spontaneous remyelination potential, is associated with an exacerbated voiding phenotype. Interestingly, while cuprizone\u2010induced CNS demyelination severely affected conscious (cortical) urinary behavior, the brainstem and spinal cord reflex remained unchanged, as confirmed by urethane\u2010anesthetized cystometry. This is the first study to show that cortical demyelination independent of inflammation can negatively impact urinary function.<\/jats:p>","DOI":"10.1002\/jnr.25065","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T02:14:28Z","timestamp":1653099268000},"page":"1707-1720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>Cuprizone\u2010mediated<\/scp>\n                    demyelination reversibly degrades voiding behavior in mice while sparing brainstem reflex"],"prefix":"10.1002","volume":"100","author":[{"given":"Ramalakshmi","family":"Ramasamy","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"UConn Center on Aging University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara C.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"UConn Center on Aging University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-1385","authenticated-orcid":false,"given":"Stephen J.","family":"Crocker","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"UConn Center on Aging University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"UConn Center on Aging University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"Department of Surgery University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u201060761\u2010720\u20104_20"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.4058"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly137"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00273.2012"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.06.038"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(03)00622\u20107"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000049644.27713.c8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.56.3.245"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00072.2015"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20105347(17)50216\u20105"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01102943"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1191\/1352458504ms1060oa"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YHBEH.2009.06.004"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090\u20104295(00)01070\u20100"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1460\u20109568.1994.TB00620.X"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1476\u20105381.2011.01302.X"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010540\u201079090\u20107_4"},{"key":"e_1_2_9_19_1","first-page":"915","volume-title":"Multiple sclerosis","author":"S\u00e8ze M.","year":"2007"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/NRN2401"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/NAU.22742"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/NRN917"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ANA.24497"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/JPET.104.076398"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)32346\u20102"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/JNNP\u20102014\u2010307712"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/NAU.24149"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1365\u20102990.2011.01168.X"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00350.2018"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNBEH.2013.00141"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22692"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/NAU.24304"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00401\u2010009\u20100591\u20103"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/JIR.2011.0072"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0320-8"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.34.5.597"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.1.65"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201047407\u2010x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0163847"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056\u20108719(01)00133\u20102"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2005.031195"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NCL.2004.09.002"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/NAU.21003"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1750\u20103639.2001.TB00385.X"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.9.3.331"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00151.2014"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3618"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5445.1265"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/1520\u20106777(2000)19:6<689::AID\u2010NAU7>3.0.CO;2\u20106"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/NRN2797"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/135245850100700404"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/NRUROL.2016.53"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/ANNUREV\u2010PATHOL\u2010011811\u2010132443"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.CON.0000433291.23091.65"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2014.10.004"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00192\u2010006\u20100131\u20109"},{"issue":"2","key":"e_1_2_9_57_1","first-page":"150","article-title":"Neuropathology of experimental allergic encephalomyelitis in inbred strains of mice","volume":"43","author":"Raine C. S.","year":"1980","journal-title":"Laboratory Investigation; A Journal of Technical Methods and Pathology"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.24654"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.24649"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/NAU.23599"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/S10286\u2010018\u20100551\u2010X"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22\u201007\u201002451.2002"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.14670\/HH\u201026.1585"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00508.2011"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/NAU.21223"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20850"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1955.182.3.572"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.DHJO.2014.10.002"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/S41983\u2010020\u201000178\u2010Z\/TABLES\/6"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100404.2008.01036.x"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x15666170717120343"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.117366"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00245.2018"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100463.2012.02882.x"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.12.004"},{"issue":"4","key":"e_1_2_9_76_1","first-page":"295","article-title":"Acute and subacute demyelination induced by mouse hepatitis virus strain A59 in C3H mice","volume":"1","author":"Woyciechowska J. L.","year":"1984","journal-title":"Journal of Experimental Pathology"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1083\/JCB.200509174"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.25065","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jnr.25065","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.25065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T07:52:34Z","timestamp":1692690754000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.25065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,20]]},"references-count":76,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1002\/jnr.25065"],"URL":"https:\/\/doi.org\/10.1002\/jnr.25065","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JNR.25065\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25065\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25065\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25065\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25065\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25065\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.25065\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,20]]},"assertion":[{"value":"2022-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}