{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:19:13Z","timestamp":1788927553761,"version":"build-2803163510"},"reference-count":193,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSERC-DG"},{"name":"CRC"},{"name":"CIHR-PG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Current pharmacological treatments for depression fail to produce adequate remission in a significant proportion of patients. Increasingly, other systems, such as the microbiome\u2013gut\u2013brain axis, are being looked at as putative novel avenues for depression treatment. Dysbiosis and dysregulation along this axis are highly comorbid with the severity of depression symptoms. The endogenous extracellular matrix protein reelin is present in all intestinal layers as well as in myenteric and submucosal ganglia, and its receptors are also present in the gut. Reelin secretion from subepithelial myofibroblasts regulates cellular migration along the crypt\u2013villus axis in the small intestine and colon. Reelin brain expression is downregulated in mood and psychotic disorders, and reelin injections have fast antidepressant-like effects in animal models of depression. This review seeks to discuss the roles of reelin in the gastrointestinal system and propose a putative role for reelin actions in the microbiota\u2013gut\u2013brain axis in the pathogenesis and treatment of depression, primarily reflecting on alterations in gut epithelial cell renewal and in the clustering of serotonin transporters.<\/jats:p>","DOI":"10.3390\/ijms25020814","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:38:51Z","timestamp":1704775131000},"page":"814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Molecular Mechanisms of Reelin in the Enteric Nervous System and the Microbiota\u2013Gut\u2013Brain Axis: Implications for Depression and Antidepressant Therapy"],"prefix":"10.3390","volume":"25","author":[{"given":"Ciara S.","family":"Halvorson","sequence":"first","affiliation":[{"name":"Division of Medical Sciences, University of Victoria, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-3574","authenticated-orcid":false,"given":"Carla Liria","family":"S\u00e1nchez-Lafuente","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Victoria, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenessa N.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0079-275X","authenticated-orcid":false,"given":"Lisa E.","family":"Kalynchuk","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Victoria, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector J.","family":"Caruncho","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Victoria, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bromet, E., Andrade, L.H., Hwang, I., Sampson, N.A., Alonso, J., de Girolamo, G., de Graaf, R., Demyttenaere, K., Hu, C., and Iwata, N. 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