Targeting dysregulated CB1 receptors in a Down syndrome mouse model improves neurological outcomes.

ABSTRACT:

Introduction

Down syndrome (DS) is the most common genetic cause of intellectual disability, affecting cognitive function and increasing the risk of early-onset Alzheimer's disease (AD). The endocannabinoid system may serve as a therapeutic target for cognitive deficits by inhibiting cannabinoid type-1 receptor (CB1R) function.

Methods

CB1R expression was analyzed in the hippocampi of aged DS-associated AD (DSAD) individuals and middle-aged Ts65Dn mice. Long-term oral treatment with the CB1R antagonist rimonabant was used to assess its effects on memory and neuroinflammation in the Ts65Dn mouse model of DS.

Results

CB1R expression was significantly increased in both aged DSAD subjects (specifically in the dentate gyrus and CA2 posterior hippocampal subregions) and Ts6

SUBMITTER: Vazquez-Oliver A 

PROVIDER: S-EPMC12628281 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature