{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:15:15Z","timestamp":1785406515346,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,20]]},"group-title":"Neuroscience","reference-count":85,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["U01AA016667"],"award-info":[{"award-number":["U01AA016667"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P50AA022537"],"award-info":[{"award-number":["P50AA022537"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AA020634"],"award-info":[{"award-number":["R01AA020634"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Studies in humans and animal models have documented relationships between initial sensitivity to alcohol and alcohol drinking behavior.<\/jats:p>\n                  <jats:p>Prior expression profiling studies of C57BL\/6J and DBA\/2J mice and rhesus macaques within the prefrontal cortex (PFC) have shown variation in myelin gene expression may be linked with alcohol sensitivity and consumption.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Combining gene expression studies from human and mouse PFC, we identified a cross-species gene network enriched for myelin-associated genes. Since myelin expression is correlated to alcohol sensitivity and alcohol drinking behavior, we hypothesized basal levels of PFC myelin gene expression may be a genomic determinant for these behavioral responses. Using an animal model of CNS demyelination, and localized knock down of N-myc downstream regulated gene 1 (\n                    <jats:italic>Ndrg1)<\/jats:italic>\n                    , we measured effects of cortical myelin reduction on initial alcohol sensitivity and drinking behavior.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Reducing myelin-related gene expression significantly altered sensitivity to alcohol and decreased alcohol consumption. Mouse genetic-based studies identified\n                    <jats:italic>Ndrg1<\/jats:italic>\n                    as a putative quantitative trait gene for sedative-hypnotic responses to alcohol. Site-specific injections of shNdrg1 lentivirus into PFC led to a significant decrease in NDRG1 expression, causing increased alcohol behavioral sensitivity and reduced preference for high concentrations of alcohol.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    Myelin is an important biological component underlying CNS disorders. Our studies demonstrate the role of a novel candidate gene (\n                    <jats:italic>Ndrg1<\/jats:italic>\n                    ), and myelin-associated gene expression, as an important factor modulating initial sensitivity to alcohol and alcohol consumption. Differences in the expression of myelin-related genes, including\n                    <jats:italic>Ndrg1<\/jats:italic>\n                    , may serve as future therapeutic targets for the treatment of alcohol use disorders.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.19.683339","type":"posted-content","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T19:50:11Z","timestamp":1760989811000},"source":"Crossref","is-referenced-by-count":0,"title":["Variation of Myelin-associated Gene Expression and\n                  <i>Ndrg1<\/i>\n                  within the Prefrontal Cortex as Determinants for Initial Level of Response to Alcohol"],"prefix":"10.64898","author":[{"given":"Jennifer T.","family":"Wolstenholme","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean 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