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Therefore, they are promising targets for studying how spinal oligodendrocyte precursor cells (OPCs) respond to injuries and neurodegenerative diseases like multiple sclerosis. Taking advantage of the temporally controlled and cell-specific genetic downregulation of GABAB receptors from OPCs, our investigation addresses their specific influence on OPC behavior in the gray and white matter of the mouse spinal cord. Our results show that, while GABAB receptors do not significantly alter spinal cord myelination under physiological conditions, they distinctly regulate the OPC differentiation and Ca2+ signaling. In addition, we investigate the impact of OPC-GABAB receptors in two models of toxic demyelination, namely, the cuprizone and the lysolecithin models. The genetic downregulation of OPC-GABAB receptors protects against demyelination and oligodendrocyte loss. Additionally, we observe the enhanced resilience to cuprizone-induced pathological alterations in OPC Ca2+ signaling. Our results provide valuable insights into the potential therapeutic implications of manipulating GABAB receptors in spinal cord OPCs and deepen our understanding of the interplay between GABAergic signaling and spinal cord OPCs, providing a basis for future research.<\/jats:p>","DOI":"10.3390\/cells13232014","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T11:27:53Z","timestamp":1733398073000},"page":"2014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic Downregulation of GABAB Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4076-2697","authenticated-orcid":false,"given":"Davide","family":"Gobbo","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0786-574X","authenticated-orcid":false,"given":"Phillip","family":"Rieder","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Pao","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3971-6845","authenticated-orcid":false,"given":"Emeline","family":"Buttigieg","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"},{"name":"Institut des Neurosciences de la Timone (INT), Aix-Marseille Universit\u00e9, CNRS UMR7289, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Schablowski","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1205-1097","authenticated-orcid":false,"given":"Elisa","family":"Damo","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bosche","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-8702","authenticated-orcid":false,"given":"Eleonora","family":"Dallorto","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"May","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, 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Gender-Specific Biology and Medicine (CGBM Chengdu), Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China"},{"name":"Experimental Research Center for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-2634","authenticated-orcid":false,"given":"Anja","family":"Scheller","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, Germany"},{"name":"Center for Gender-Specific Biology and Medicine (CGBM), Saarland University, 66421 Homburg, 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