genetic analysis of the neurosteroid deoxycorticosterone and its relation to alcohol phenotypes identification of qtls and downstream gene regulation遗传分析的neurosteroid去氧皮质酮及其涉及的qtl与酒精表型鉴定和下游基因调控.pdfVIP

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genetic analysis of the neurosteroid deoxycorticosterone and its relation to alcohol phenotypes identification of qtls and downstream gene regulation遗传分析的neurosteroid去氧皮质酮及其涉及的qtl与酒精表型鉴定和下游基因调控.pdf

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genetic analysis of the neurosteroid deoxycorticosterone and its relation to alcohol phenotypes identification of qtls and downstream gene regulation遗传分析的neurosteroid去氧皮质酮及其涉及的qtl与酒精表型鉴定和下游基因调控

Genetic Analysis of the Neurosteroid Deoxycorticosterone and Its Relation to Alcohol Phenotypes: Identification of QTLs and Downstream Gene Regulation 1,2 2 2 3 4 4 Patrizia Porcu *, Todd K. O’Buckley , Soomin C. Song , Jo Lynne Harenza , Lu Lu , Xusheng Wang , 4 3 1,2,5 Robert W. Williams , Michael F. Miles , A. Leslie Morrow 1 Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America, 2 Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America, 3 Departments of Neurology and Pharmacology/Toxicology and The Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia, United States of America, 4 Department of Anatomy and Neurobiology and Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America, 5 Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America Abstract Background: Deoxycorticosterone (DOC) is an endogenous neurosteroid found in brain and serum, precursor of the GABAergic neuroactive steroid (3a,5a)-3,21-dihydroxypregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) and the glucocorticoid corticosterone. These steroids are elevated following stress or ethanol administration, contribute to ethanol sensitivity, and their elevation is blunted in ethanol dependence. Methodology/Principal Findings: To systematically define the genetic basis, regulation, and beh