Astrocytes in the Circadian System: A Promising Target for Mood Disorder Interventions

Circadian rhythms and emotional health are fundamentally interconnected. Circadian rhythms are characterized by self-sustaining oscillations within biological systems that synchronize sleep-wake cycles and related physiological and biochemical processes with periodic environmental changes. Clinical observations have demonstrated the significant role of the biological clock in the regulation of mood and anxiety, indicating that disruptions in circadian pacemaker control may contribute to the development of mood disorders and psychopathology. Conversely, therapeutic interventions aimed at correcting circadian misalignment have been shown to alleviate symptoms of mood disorders. The mechanistic involvement of astrocytes in mood disorders has been well-established. Recent research indicates that astrocytes possess the ability to autonomously regulate circadian rhythms, independent of pacemaker neurons. In addition to modulating rhythmicity in the central pacemaker, the suprachiasmatic nucleus (SCN), astrocytes are involved in circadian regulation within emotion-related brain regions, such as the nucleus accumbens (NAc) and amygdala. Nonetheless, the precise mechanisms by which astrocytes influence mood through circadian pathways, and the potential for their rhythmic alterations to serve as therapeutic targets for mood disorders, remain incompletely understood. In this review we synthesizes contemporary evidence regarding the role of astrocytes as pivotal regulators of circadian rhythms, focusing on how their intrinsic transcriptional-translational feedback loop (TTFL) oscillations influence mood disorders. Additionally, we investigate the role of astrocytic neurotransmitters, such as glutamate, γ-aminobutyric acid (GABA), and purinergic signaling, in the circadian-mediated amelioration of mood pathologies. These insights offer novel perspectives for identifying chronotherapeutic intervention targets for mood disorders.