{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:00Z","timestamp":1787013780228,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,12,7]],"date-time":"2015-12-07T00:00:00Z","timestamp":1449446400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes on Alcohol Abuse and Alcoholism at the National Institutes of Health","award":["AA-11431"],"award-info":[{"award-number":["AA-11431"]}]},{"name":"National Institutes on Alcohol Abuse and Alcoholism at the National Institutes of Health","award":["AA-12908"],"award-info":[{"award-number":["AA-12908"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alcohol\u2010mediated neurodegeneration is associated with white matter (\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      ) atrophy due to targeting of myelin and oligodendrocytes. However, variability in disease severity suggests cofactors contribute to\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      degeneration. We examined the potential cofactor role of the tobacco\u2010specific nitrosamine, nicotine\u2010derived nitrosamine ketone (\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      ), because smoking causes\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      atrophy and most heavy drinkers consume tobacco products.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This 8\u2010week study of Long Evans rats had 4 treatment groups: control;\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      \u20102\u00a0mg\/kg, 3\u00d7\/wk in weeks 3 to 8; ethanol (EtOH) (chronic\u201026% caloric\u00a0+\u00a0binge\u20102\u00a0g\/kg, 3\u00d7\/wk in weeks 7 to 8); and EtOH\u00a0+\u00a0\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      . Exposure effects on\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      lipid biochemical profiles and in\u00a0situ distributions were examined using matrix\u2010assisted laser desorption\/ionization imaging mass spectrometry and tandem mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      mainly caused\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      fiber degeneration and fiber loss, EtOH caused demyelination, and dual exposures had additive effects. EtOH and EtOH\u00a0+\u00a0\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      decreased\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      (including corpus callosum) and\/or gray matter (hypothalamus, cortex, medial temporal) levels of several phosphatidylserine, phosphatidylinositol, and sphingolipid (sulfatide [ST]) species, while\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      increased or had minimal effect on these lipids. EtOH\u00a0+\u00a0\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      had broader and larger inhibitory effects on phospholipids and ST than EtOH or\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      alone. Principal component analysis clustered control with\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      , and EtOH with EtOH\u00a0+\u00a0\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      groups, highlighting the independent EtOH\u2010 rather than\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      \u2010driven responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Chronic EtOH exposures decreased several phospholipid and sphingolipid species in brain, while concomitant\n                      <jats:styled-content style=\"fixed-case\">NNK<\/jats:styled-content>\n                      exposures exacerbated these effects. These findings support our hypothesis that tobacco smoking is a pathogenic cofactor in alcohol\u2010mediated\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      degeneration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.12909","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T04:57:17Z","timestamp":1450760237000},"page":"2324-2333","source":"Crossref","is-referenced-by-count":32,"title":["Differential Sphingolipid and Phospholipid Profiles in Alcohol and Nicotine\u2010Derived Nitrosamine Ketone\u2010Associated White Matter Degeneration"],"prefix":"10.1111","volume":"39","author":[{"given":"Emine B.","family":"Yalcin","sequence":"first","affiliation":[{"name":"Liver Research Center Division of Gastroenterology Department of Medicine Rhode Island Hospital and the Alpert Medical School of Brown University Providence Rhode Island"},{"name":"Rhode 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