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Moreover, ECS failure has been proposed to mediate the cognitive impairment and \u03b2\u2010amyloid production in Alzheimer disease (AD). Thus, in the present study, we evaluated the effects of adolescent EtOH binge drinking on the cognitive disturbances, hippocampal \u03b2\u2010amyloid levels, and in the ECS expression on a transgenic mouse model (APP\/PSEN, AZ) of AD. We exposed AZ and wild\u2010type mice to a binge\u2010drinking treatment during adolescence. At 6 and 12 months of age, we evaluated hippocampal\u2010dependent learning and memory: \u03b2\u2010amyloid concentrations and RNA and protein levels of cannabinoid type\u20102 receptors (CB2), diacylglycerol lipase\u2010\u03b1 (DAGL\u03b1), and monoacylglycerol lipase (MAGL) in the hippocampus. The results showed that binge\u2010EtOH treatment worsens cognitive function and increases \u03b2\u2010amyloid levels in AZ. At 6 months, EtOH heightens CB2 (RNA and protein) and DAGL\u03b1 (RNA) expression in wild type but not in AZ. On the contrary, EtOH enhances MAGL RNA expression only in AZ. At 12 months, AZ displays increased levels of CB2 (RNA and protein) and DAGL\u03b1 (protein) compared with control. Similar to what happens at 6 months, EtOH induces an increase in CB2 gene expression in wild type but not in AZ; however, it augments CB2 and DAGL\u03b1 protein levels in both genotypes. Therefore, we propose that adolescent binge drinking accelerates cognitive deficits associated with aging and AD. It also accelerates hippocampal \u03b2\u2010amyloid accumulation in AZ and affects differently the ECS response in wild type and AZ.<\/jats:p>","DOI":"10.1111\/adb.12883","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T12:03:53Z","timestamp":1581422633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Adolescent binge\u2010ethanol accelerates cognitive impairment and \u03b2\u2010amyloid production and dysregulates endocannabinoid signaling in the hippocampus of APP\/PSE mice"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-2842","authenticated-orcid":false,"given":"Juan Carlos","family":"Ledesma","sequence":"first","affiliation":[{"name":"Departament de Psicobiologia Universitat de Val\u00e8ncia  Valencia 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