{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:16:28Z","timestamp":1781187388269,"version":"3.54.1"},"reference-count":98,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T00:00:00Z","timestamp":1651968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Alcohol Abuse and Alcoholism (NIAAA)","award":["AA-011431"],"award-info":[{"award-number":["AA-011431"]}]},{"name":"National Institute of Alcohol Abuse and Alcoholism (NIAAA)","award":["AA-028408"],"award-info":[{"award-number":["AA-028408"]}]},{"name":"National Institute of Alcohol Abuse and Alcoholism (NIAAA)","award":["AA024092"],"award-info":[{"award-number":["AA024092"]}]},{"name":"National Institute of Alcohol Abuse and Alcoholism (NIAAA)","award":["AA-12908"],"award-info":[{"award-number":["AA-12908"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Alcohol-related brain degeneration is linked to cognitive-motor deficits and impaired signaling through insulin\/insulin-like growth factor type 1 (IGF-1)-Akt pathways that regulate cell survival, plasticity, metabolism, and homeostasis. In addition, ethanol inhibits Aspartyl-asparaginyl-\u03b2-hydroxylase (ASPH), a downstream target of insulin\/IGF-1-Akt signaling and an activator of Notch networks. Previous studies have suggested that early treatment with insulin sensitizers or dietary soy could reduce or prevent the long-term adverse effects of chronic ethanol feeding. Objective: The goal of this study was to assess the effects of substituting soy isolate for casein to prevent or reduce ethanol\u2019s adverse effects on brain structure and function. Methods: Young adolescent male and female Long Evans were used in a 4-way model as follows: Control + Casein; Ethanol + Casein; Control + Soy; Ethanol + Soy; Control = 0% ethanol; Ethanol = 26% ethanol (caloric). Rats were fed isocaloric diets from 4 to 11 weeks of age. During the final experimental week, the Morris Water maze test was used to assess spatial learning (4 consecutive days), after which the brains were harvested to measure the temporal lobe expression of the total phospho-Akt pathway and downstream target proteins using multiplex bead-based enzyme-linked immunosorbent assays (ELISAs) and duplex ELISAs. Results: Ethanol inhibited spatial learning and reduced brain weight, insulin signaling through Akt, and the expression of ASPH when standard casein was provided as the protein source. The substitution of soy isolate for casein largely abrogated the adverse effects of chronic ethanol feeding. In contrast, Notch signaling protein expression was minimally altered by ethanol or soy isolate. Conclusions: These novel findings suggest that the insulin sensitizer properties of soy isolate may prevent some of the adverse effects that chronic ethanol exposure has on neurobehavioral function and insulin-regulated metabolic pathways in adolescent brains.<\/jats:p>","DOI":"10.3390\/biom12050676","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T08:04:21Z","timestamp":1651997061000},"page":"676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Dietary Soy Prevents Alcohol-Mediated Neurocognitive Dysfunction and Associated Impairments in Brain Insulin Pathway Signaling in an Adolescent Rat Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Ming","family":"Tong","sequence":"first","affiliation":[{"name":"Liver Research Center, Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02808, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Ziplow","sequence":"additional","affiliation":[{"name":"Liver Research Center, Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02808, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Princess","family":"Mark","sequence":"additional","affiliation":[{"name":"Liver Research Center, Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02808, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"de la Monte","sequence":"additional","affiliation":[{"name":"Liver Research Center, Division of Gastroenterology, Departments of Medicine, Neurology and Pathology and Laboratory Medicine, Rhode Island Hospital, Providence, RI 02808, USA"},{"name":"Women and Infants Hospital of Rhode Island, Alpert Medical School of Brown University, Providence VA Medical Center, Providence, RI 02808, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/sj.npp.1301219","article-title":"Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning","volume":"32","author":"Chanraud","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1111\/j.1440-1746.2007.05298.x","article-title":"Quantifying the risk for alcohol-use and alcohol-attributable health disorders: Present findings and future research needs","volume":"23","author":"Li","year":"2008","journal-title":"J. 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