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Although remyelination can occur, regeneration in adults is often limited, resulting in incomplete repair and impaired nerve function. In multiple sclerosis (MS), an immune-mediated demyelinating disease with diverse clinical phenotypes, progression and disability correlate with demyelination and failed remyelination, influenced by genetic and environmental factors. A well-established method to study MS-like demyelination and its cellular and molecular mechanisms utilizes cuprizone (CPZ), extensively studied in adult rodents. Although early-onset demyelination often causes lifelong disability, its pathophysiology remains poorly understood, underscoring the need for models to dissect its biological features. Here, we characterized the effects of early-age CPZ-induced demyelination in juvenile na\u00efve mice, focusing on region-specific vulnerability and neuroinflammatory responses. One-month-old mice were exposed to 0.2% CPZ for five weeks, followed by behavioral, cellular, and transcriptomic analyses. Susceptibility to the early-exposure of CPZ varied between the analysed brain regions. The midline corpus callosum and motor cortex were highly vulnerable, showing marked reductions in myelin together with elevated microglial activation. Other regions, including the hippocampus and amygdala, showed milder susceptibility, often restricted to changes in\n                    <jats:italic>Mbp<\/jats:italic>\n                    or\n                    <jats:italic>Iba1<\/jats:italic>\n                    transcript levels without corresponding alterations in oligodendrocyte or microglial cell numbers. Behaviorally, early CPZ exposure reduced locomotor activity but did not produce robust anxiety-like or cognitive deficits. Together, these findings reveal distinct regional patterns of early-onset demyelination and neuroinflammation and support CPZ exposure in juvenile mice as a relevant model for multifocal juvenile demyelination, including paediatric-onset MS, and its impact on neurodevelopment.\n                  <\/jats:p>","DOI":"10.1007\/s12017-026-08911-2","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:12:53Z","timestamp":1772709173000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Early-Age Cuprizone Exposure Induces Region-Specific Demyelination and Neuroinflammation in Mice"],"prefix":"10.1007","volume":"28","author":[{"given":"May","family":"Rokach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilad","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galit","family":"Elad-Sfadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boaz","family":"Barak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"8911_CR1","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s42000-020-00197-8","volume":"19","author":"M Anagnostouli","year":"2020","unstructured":"Anagnostouli, M., Markoglou, N., & Chrousos, G. 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