Altered glial expression of the cannabinoid 1 receptor in the subiculum of a mouse model of Alzheimer's disease.

The alteration of the endocannabinoid tone usually associates with changes in the expression and/or function of the cannabinoid CB 1 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 CB 1 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 CB 1 receptor localization in both glial cells was investigated in the subiculum of male 5xFAD/CB 2 EGFP/f/f (AD model) and CB 2 EGFP/f/f mice by immuno-electron microscopy. The findings revealed that glial CB 1 receptors suffer remarkable changes in the AD mouse. Thus, CB 1 receptor expression increases in reactive microglia in 5xFAD/CB 2 EGFP/f/f , but remains constant in astrocytes with CB 1 receptor labeling rising proportionally to the perimeter of the reactive astrocytes. Not least, the CB 1 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 CB 1 receptor in microglia. These findings on the correlation between glial reactivity and the CB 1 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.