{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:57:19Z","timestamp":1789520239274,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Gut inflammation is a salient prodromal feature of Parkinson's disease (PD) implicated in pathologic processes leading to nigrostriatal dopaminergic degeneration. However, existing rodent models of PD are suboptimal for investigating the interaction between gut inflammation and neuropathology. This study aimed to develop a rat model of PD in which gut inflammation exacerbated PD symptoms induced by a parkinsonian lesion. This was achieved by combining the 6\u2010hydroxydopamine (6\u2010OHDA) rat model for PD and the dextran sodium sulfate (DSS) rat model for colitis. The model was characterised using behavioural tests, including reaching, step, gait, open\u2010field and cylinder tests, plus stereological quantification of substantia nigra (SN) DA neurodegeneration, and histological analysis of SN microglial activation and distal colon morphology. The combination of 6\u2010OHDA and DSS resulted in greater stool softening and bleeding, shorter colons and greater distal colon histological damage, when compared with the 6\u2010OHDA model. Additionally, 6\u2010OHDA and DSS rats displayed similar DA neurodegeneration, yet less SN microglial activation, when compared to 6\u2010OHDA rats that did not receive DSS. Finally, DSS\u2009+\u20096\u2010OHDA rats exhibited impaired forelimb motor function compared with 6\u2010OHDA rats, with decreased performance in reaching and step tests. In conclusion, DSS administration exacerbated forelimb motor dysfunction in 6\u2010OHDA rats. Behavioural changes in DSS\u2009+\u20096\u2010OHDA rats were associated with lower levels of microglial activation and similar levels of dopamine depletion compared with 6\u2010OHDA\u2010only rats. These results support that the DSS\u2009+\u20096\u2010OHDA rat model is a promising PD animal model to investigate deleterious gut\u2013brain interactions in PD.<\/jats:p>","DOI":"10.1111\/ejn.16667","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T01:45:16Z","timestamp":1737596716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Rat Model for Inflammatory Gut\u2013Brain Interactions in Parkinson's Disease"],"prefix":"10.1111","volume":"61","author":[{"given":"Grace\u00a0E.","family":"Kendall","sequence":"first","affiliation":[{"name":"Department of Anatomy, Brain Health Research Centre University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor\u00a0F.","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Brain Health Research Centre University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-7669","authenticated-orcid":false,"given":"Louise\u00a0C.","family":"Parr\u2010Brownlie","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Brain Health Research Centre University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1767203"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.6A7156.2007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.05.010"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00218-X"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328305bdaf"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0893-14.2014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjparkd.2015.14"},{"issue":"3","key":"e_1_2_10_9_1","first-page":"240","article-title":"Hepatic Encephalopathy","volume":"27","author":"Butterworth R. 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