Understanding the Role of the Circadian Clock Gene Bmal1 in Astrocytes

Abstract

The endogenous circadian rhythms in mammals are driven by a network of clock genes. These clock genes in turn regulate behavioral and physiological changes that follow a rhythm of approximately 24 hours. It is known that the brain region, the suprachiasmatic nucleus (SCN) in the hypothalamus, is essential to maintain the body circadian rhythm. The role of the neuronal cells in this circadian rhythm has been studied extensively. However, recent studies have shown a circadian rhythmicity in glial cells, such as the astrocytes, as well. This study is intended to add to the growing body of knowledge on the role of glial cells in circadian rhythm beyond the original idea that the central circadian pacemaker of mammals is solely driven by neurons. Based on prior studies in this laboratory and others, I hypothesize that the lack of Bmal1, a core clock gene, in astrocytes will impact circadian rhythmicity, at the molecular level (gene expression via assessment of core clock gene Per2 expression) as well as in terms of whole animal behavior (running wheel activity on different lighting regimens). Our studies indicate there is a loss of rhythm in astrocyte culture knock outs, but rhythm is maintained when analyzing locomotor activity. This suggests the gene in astrocytes may not be essential to maintain circadian rhythmicity. Understanding the role of the glial cells in circadian rhythmicity in mice, may help understand their role in circadian disorders. That in turn may help treat diseases that are correlated with chronic disruption of the circadian clock; such as diabetes, some cardiovascular diseases, and cancer.