Molecular Rhythmicity in Glia: Importance for Brain Health and Relevance to Psychiatric Disease

Abstract

Circadian rhythms are approximate 24-hour rhythms present in nearly all aspects of human physiology, including proper brain function. These rhythms are produced at the cellular level through a transcriptional-translational feedback loop known as the molecular clock. Diurnal variation in gene expression has been demonstrated in brain tissue from multiple species, including humans, in both cortical and subcortical regions. Interestingly, these rhythms in gene expression have been shown to be disrupted across psychiatric disorders and may be implicated in their underlying pathophysiology. However, little is known regarding molecular rhythms in specific cell types in the brain and how they might be involved in psychiatric disease. Although glial cells (e.g., astrocytes, microglia, and oligodendrocytes) have been historically understudied compared to neurons, evidence of the molecular clock is found within each of these cell subtypes. Here, we review the current literature, which suggests that molecular rhythmicity is essential to functional physiologic outputs from each glial subtype. Furthermore, disrupted molecular rhythms within these cells and the resultant functional deficits may be relevant to specific phenotypes across psychiatric illnesses. Given that circadian rhythm disruptions have been so integrally tied to psychiatric disease, the molecular mechanisms governing these associations could represent exciting new avenues for future research and potential novel pharmacologic targets for treatment.

Keywords: astrocytes; microglia; mood disorders; oligodendrocytes; schizophrenia; substance use disorders.