Faculty Collaboration Database

Altered glial expression of the cannabinoid 1 receptor in the subiculum of a mouse model of Alzheimer's disease. Glia 2023 Apr;71(4):866-879

Date

11/29/2022

Pubmed ID

36437738

DOI

10.1002/glia.24312

Scopus ID

2-s2.0-85142903688 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

The alteration of the endocannabinoid tone usually associates with changes in the expression and/or function of the cannabinoid CB₁ receptor. In Alzheimer's disease (AD), amyloid beta (Aβ)-containing aggregates induce a chronic inflammatory response leading to reactivity of both microglia and astrocytes. However, how this glial response impacts on the glial CB₁ receptor expression in the subiculum of a mouse model of AD, a brain region particularly affected by large accumulation of plaques and concomitant subcellular changes in microglia and astrocytes, is unknown. The CB₁ receptor localization in both glial cells was investigated in the subiculum of male 5xFAD/CB₂ ^EGFP/f/f (AD model) and CB₂ ^EGFP/f/f mice by immuno-electron microscopy. The findings revealed that glial CB₁ receptors suffer remarkable changes in the AD mouse. Thus, CB₁ receptor expression increases in reactive microglia in 5xFAD/CB₂ ^EGFP/f/f , but remains constant in astrocytes with CB₁ receptor labeling rising proportionally to the perimeter of the reactive astrocytes. Not least, the CB₁ receptor localization in microglial processes in the subiculum of controls and closely surrounding amyloid plaques and dystrophic neurites of the AD model, supports previous suggestions of the presence of the CB₁ receptor in microglia. These findings on the correlation between glial reactivity and the CB₁ receptor expression in microglial cells and astrocytes, contribute to the understanding of the role of the endocannabinoid system in the pathophysiology of Alzheimer's disease.

Author List

Terradillos I, Bonilla-Del Río I, Puente N, Serrano M, Mimenza A, Lekunberri L, Anaut-Lusar I, Reguero L, Gerrikagoitia I, Ruiz de Martín Esteban S, Hillard CJ, Grande MT, Romero J, Elezgarai I, Grandes P

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alzheimer Disease
Amyloid beta-Peptides
Animals
Cannabinoids
Disease Models, Animal
Endocannabinoids
Hippocampus
Male
Mice
Mice, Transgenic
Microglia
Neuroglia
Plaque, Amyloid
Receptors, Cannabinoid