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It has been demonstrated that ketamine induces alterations in extracellular matrix (ECM) in rodent models which in part plays a role in its anti-depressant action. The nematode<jats:italic>Caenorhabditis elegans<\/jats:italic>serves as a powerful tool for understanding mechanisms of drug action with its short life cycle, genetic amenability and conserved cellular processes. Further investigation is required particularly in in vivo systems to gain broader understanding of ketamine\u2019s actions. In this study, we aimed to decipher ketamine-mediated alterations using<jats:italic>C. elegans<\/jats:italic>as a model. We show that ketamine specifically induces apical extracellular matrix modifications (aECM) in the vulva and the cuticle. Ketamine treatment phenocopies neuronal migration and vulval invagination defects of chondroitin mutants despite wild-type like chondroitin staining pattern. Normal vulval expansion and defective vulval eversion phenotypes of ketamine-treated animals are suggestive of alterations in the network of aECM factors which do not impinge on chondroitin. Ketamine ameliorates impaired movement of a group of<jats:italic>roller<\/jats:italic>mutants characterised with collagen defects in the cuticle and RNA-seq identifies that 30% of the cuticular collagens are upregulated in response to ketamine. Ketamine alters aECM, neuronal migration and collagen expression in<jats:italic>C. elegans<\/jats:italic>. We propose<jats:italic>C. elegans<\/jats:italic>as a putative animal model to investigate ketamine-mediated ECM modifications.<\/jats:p>","DOI":"10.1038\/s41598-022-24632-5","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T18:03:56Z","timestamp":1671645836000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ketamine induces apical extracellular matrix modifications in Caenorhabditis elegans"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-2650","authenticated-orcid":false,"given":"Duygu","family":"Y\u00fccel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"24632_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0006-3223(99)00230-9","volume":"47","author":"RM Berman","year":"2000","unstructured":"Berman, R. 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