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Astroglial CB1 receptors, energy metabolism, and gliotransmission: an integrated signaling system?

Journal

ESSAYS IN BIOCHEMISTRY
Volume 67, Issue 1, Pages 49-62

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/EBC20220089

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Astrocytes play a crucial role in brain homeostasis and function, responding to neuronal signals and modulating synaptic activity through gliotransmission. The cannabinoid type-1 (CB1) receptor has emerged as a critical player in the control of glio-transmission and metabolic cooperation between astrocytes and neurons. This review discusses the known and newly discovered properties of astroglial CB1 receptors and their impact on brain function and behavior, highlighting the interconnected relationship between energy metabolism and gliotransmission.
Astrocytes are key players in brain homeostasis and function. During the last years, several studies have cemented this notion by showing that these cells respond to neuronal signals and, via the release of molecules that modulate and support synaptic activity (gliotrans-mission) participates in the functions of the so-called tripartite synapse. Thus, besides their established control of brain metabolism, astrocytes can also actively control synaptic activity and behavior. Among the signaling pathways that shape the functions of astrocyte, the cannabinoid type-1 (CB1) receptor is emerging as a critical player in the control of both glio-transmission and the metabolic cooperation between astrocytes and neurons. In the present short review, we describe known and newly discovered properties of the astroglial CB1 receptors and their role in modulating brain function and behavior. Based on this evidence, we finally discuss how the functions and mode of actions of astrocyte CB1 receptors might represent a clear example of the inextricable relationship between energy metabolism and gliotransmission. These tight interactions will need to be taken into account for future research in astrocyte functions and call for a reinforcement of the theoretical and experimental bridges between studies on metabolic and synaptic functions of astrocytes.

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