当前位置： SCI文献检索 > ADDICTION BIOLOGY期刊下所有文献 > Adolescent binge-ethanol accelerates cognitive impairment and β-amyloid production and dysregulates endocannabinoid signaling in the hippocampus of APP/PSE mice.

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

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.

journal_name

Addict Biol

journal_title

Addiction biology

authors

Ledesma JC,Rodríguez-Arias M,Gavito AL,Sánchez-Pérez AM,Viña J,Medina Vera D,Rodríguez de Fonseca F,Miñarro J

doi

10.1111/adb.12883

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

e12883

issue

eissn

1355-6215

issn

1369-1600

journal_volume

pub_type

杂志文章

在线工具

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