Adolescent binge‐ethanol accelerates cognitive impairment and β‐amyloid production and dysregulates endocannabinoid signaling in the hippocampus of APP/PSE mice

Authors:
Publisher website
Google Scholar
Abstract
Previous research in rodents suggests that the long‐term neurobehavioral disturbances induced by chronic ethanol (EtOH) exposure could be due to endocannabinoid system (ECS) alterations. Moreover, ECS failure has been proposed to mediate the cognitive impairment and β‐amyloid production in Alzheimer disease (AD). Thus, in the present study, we evaluated the effects of adolescent EtOH binge drinking on the cognitive disturbances, hippocampal β‐amyloid levels, and in the ECS expression on a transgenic mouse model (APP/PSEN, AZ) of AD. We exposed AZ and wild‐type mice to a binge‐drinking treatment during adolescence. At 6 and 12 months of age, we evaluated hippocampal‐dependent learning and memory: β‐amyloid concentrations and RNA and protein levels of cannabinoid type‐2 receptors (CB2), diacylglycerol lipase‐α (DAGLα), and monoacylglycerol lipase (MAGL) in the hippocampus. The results showed that binge‐EtOH treatment worsens cognitive function and increases β‐amyloid levels in AZ. At 6 months, EtOH heightens CB2 (RNA and protein) and DAGLα (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 DAGLα (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 DAGLα protein levels in both genotypes. Therefore, we propose that adolescent binge drinking accelerates cognitive deficits associated with aging and AD. It also accelerates hippocampal β‐amyloid accumulation in AZ and affects differently the ECS response in wild type and AZ.
Funding Information
  • RETICS Red de Trastornos Adictivos, Instituto de Salud Carlos III ((JM and MRA RD16/0017/0007; FRF: RD16/0017/0001), Fatzheimer project EULAC-HEALTH H2020 (EULACH16/, Ministerio de Economía y Competitividad (MINECO),)

This publication has 48 references indexed in Scilit: