{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:22:46Z","timestamp":1753878166352,"version":"3.41.2"},"reference-count":142,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The early initiation of binge\u2010drinking and biological sex are critical risk factors for the development of affective disturbances and cognitive decline, as well as neurodegenerative diseases including Alzheimer's disease. Further, a history of excessive alcohol consumption alters normal age\u2010related changes in the pattern of protein expression in the brain, which may relate to an acceleration of cognitive decline. Here, we aimed to disentangle the interrelation between a history of binge\u2010drinking during adolescence, biological sex and normal aging on the manifestation of negative affect, cognitive decline and associated biochemical pathology. To this end, adolescent male and female C57BL\/6J mice (PND 28\u201329) underwent 30 days of alcohol binge\u2010drinking using a modified drinking\u2010in\u2010the\u2010dark (DID) paradigm. Then, mice were assayed for negative affect, sensorimotor gating and cognition at three developmental stages during adulthood\u2014mature adulthood (6\u00a0months), pre\u2010middle age (9\u00a0months) and middle age (12\u2009months). Behavioural testing was then followed by immunoblotting to index the protein expression of glutamate receptors, neuropathological markers [Tau, p (Thr217)\u2010Tau, p (Ser396)\u2010Tau, BACE, APP, A\u03b2], as well as ERK activation within the entorhinal cortex, prefrontal cortex and amygdala. Across this age span, we detected only a few age\u2010related changes in our measures of negative affect or spatial learning\/memory in the Morris water maze and all of these changes were sex\u2010specific. Prior adolescent binge\u2010drinking impaired behaviour only during reversal learning in 9\u2010month\u2010old females and during radial arm maze testing in 12\u2010month\u2010old females. In contrast to behaviour, we detected a large number of protein changes related to prior binge\u2010drinking history, several of which manifested as early as 6\u00a0months of age, with the prefrontal cortex particularly affected at this earlier age. While 6\u2010month\u2010old mice exhibited relatively few alcohol\u2010related protein changes within the entorhinal cortex and amygdala, the number of alcohol\u2010related protein changes within the entorhinal cortex increased with age, while the 12\u2010month\u2010old mice exhibited the largest number of protein changes within the amygdala. Approximately a third of the alcohol\u2010related protein changes were sex\u2010selective. Taken together, the results of our longitudinal study using a murine model of binge\u2010drinking indicate that a prior history of heavy alcohol consumption, beginning in adolescence, is sufficient to induce what we presume to be latent changes in protein indices of cellular activity, glutamate transmission and neuropathology within key brain regions governing cognition, executive function and emotion that appear to precede the onset of robust behavioural signs of dysregulated affect and cognitive impairment.<\/jats:p>","DOI":"10.1111\/adb.70006","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T12:40:30Z","timestamp":1734007230000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biochemical changes precede affective and cognitive anomalies in aging adult C57BL\/6J mice with a prior history of adolescent alcohol binge\u2010drinking"],"prefix":"10.1111","volume":"29","author":[{"given":"C. Leonardo Jimenez","family":"Chavez","sequence":"first","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0226-1567","authenticated-orcid":false,"given":"Gavin P.","family":"Scheldrup","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren E.","family":"Madory","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J. 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose","family":"Torres\u2010Gonzales","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica N.","family":"Herbert","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Kotlyar","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neda","family":"Riazat","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Pakter","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliyanna","family":"Van Doren","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Ter Galstian","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1078-1077","authenticated-orcid":false,"given":"Karen K.","family":"Szumlinski","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"},{"name":"Department of Molecular, Cellular and Developmental Biology University of California Santa Barbara  Santa Barbara California USA"},{"name":"Neuroscience Research Institute University of California Santa Barbara  Santa Barbara California USA"},{"name":"Center for Aging and Longevity Studies University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_8_2_1","DOI":"10.1016\/j.jadohealth.2006.05.014"},{"doi-asserted-by":"publisher","key":"e_1_2_8_3_1","DOI":"10.1016\/j.tics.2004.12.008"},{"volume-title":"The behavioral neuroscience of adolescence","year":"2010","author":"Spear L","key":"e_1_2_8_4_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_5_1","DOI":"10.1038\/npp.2009.110"},{"doi-asserted-by":"publisher","key":"e_1_2_8_6_1","DOI":"10.1016\/j.pbb.2015.03.015"},{"doi-asserted-by":"publisher","key":"e_1_2_8_7_1","DOI":"10.1007\/0\u2010306\u201048626\u20101_7"},{"volume-title":"Binge drinking (past 30 days) by year, grades 9\u201312, New Mexico and U.S., 2001 to 2017","year":"2022","author":"New Mexico Department of Health (NM\u2010IBIS)","key":"e_1_2_8_8_1"},{"volume-title":"Drinking levels 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