{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:25:25Z","timestamp":1783297525942,"version":"3.54.6"},"reference-count":58,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001061","name":"Rebecca L. Cooper Medical Research Foundation","doi-asserted-by":"publisher","award":["PG2020710"],"award-info":[{"award-number":["PG2020710"]}],"id":[{"id":"10.13039\/501100001061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuroprotective and anti-inflammatory molecules of the central nervous system (CNS). Both bind to three G protein-coupled receptors, namely PAC1, VPAC1 and VPAC2, to elicit their beneficial effects in various CNS diseases, including multiple sclerosis (MS). In this study, we assessed the expression and distribution of PACAP\/VIP receptors in the normal-appearing white matter (NAWM) of MS donors with a clinical history of either relapsing\u2013remitting MS (RRMS), primary MS (PPMS), secondary progressive MS (SPMS) or in aged-matched non-MS controls. Gene expression studies revealed MS-subtype specific changes in PACAP and VIP and in the receptors\u2019 levels in the NAWM, which were partly corroborated by immunohistochemical analyses. Most PAC1 immunoreactivity was restricted to myelin-producing cells, whereas VPAC1 reactivity was diffused within the neuropil and in axonal bundles, and VPAC2 in small vessel walls. Within and around lesioned areas, glial cells were the predominant populations showing reactivity for the different PACAP\/VIP receptors, with distinctive patterns across MS subtypes. Together, these data identify the differential expression patterns of PACAP\/VIP receptors among the different MS clinical entities. These results may offer opportunities for the development of personalized therapeutic approaches to treating MS and\/or other demyelinating disorders.<\/jats:p>","DOI":"10.3390\/ijms25168850","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T09:20:51Z","timestamp":1723627251000},"page":"8850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential Expression of PACAP\/VIP Receptors in the Post-Mortem CNS White Matter of Multiple Sclerosis Donors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0721-4055","authenticated-orcid":false,"given":"Margo Iris","family":"Jansen","sequence":"first","affiliation":[{"name":"Laboratory of Cellular & Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, P.O. Box 123, Sydney, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-8890","authenticated-orcid":false,"given":"Giuseppe","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7037-759X","authenticated-orcid":false,"given":"Alessandro","family":"Castorina","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular & Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, P.O. Box 123, Sydney, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dargahi, N., Katsara, M., Tselios, T., Androutsou, M.E., de Courten, M., Matsoukas, J., and Apostolopoulos, V. (2017). Multiple Sclerosis: Immunopathology and Treatment Update. 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