Interplay Between Astroglial Endocannabinoid System and the Cognitive Dysfunction in Alzheimer's Disease

Abstract

Cannabinoid CB1 receptors have been shown to regulate wide array of functions ranging from homeostasis to the cognitive functioning but recent data support the hypothesis that astrocytes also operate as a mediator of synaptic plasticity and contribute to cognition and learning. The receptor heterogeneity plays a key role in understanding the molecular mechanisms underlying these processes. Despite the fact that the majority of CB1 receptors act on neurons, studies have revealed that cannabinoids have direct control over astrocytes, including energy generation and neuroprotection. The tripartite synapse connects astrocytes to neurons and allows them to interact with one another and the astrocytes are key players in synaptic plasticity, which is associated with cognitive functions. This review focuses on our growing understanding of the intricate functions of astroglial CB1 that underpin physiological brain function, and in Alzheimer's disease.

Fig. 1

Astrocyte physiological functions and the formation of tripartite synapse with intercellular communications. Arrows in black indicates facilitatory affect. The image was created on Biorender.com under paid subscription.

Fig. 2

Endocannabinoid signalling in neuronal communication and the mechanism involved in the induction of LTD. Arrows in black indicates facilitatory affect and red arrows indicates inhibitory actions. The image was created on Biorender.com under paid subscription.