Abstract

Most organisms possess biological pacemakers that generate daily oscillations ranging from molecular processes to rhythms in physiology and behavior. In mammals, this system is composed of a master clock, located in the Suprachiasmatic Nucleus (SCN), and several peripheral clocks found in various tissues and brain regions. Previously, it has been identified that genome-wide or tissue-specific disruptions of circadian clock-genes such as Bmal1 are associated with mood disorders. Particularly in the striatum, a brain region that is vital in the motor and reward systems. Interestingly, the exact underlying molecular mechanisms are not well understood. In this study, gene expression of the receptors corresponding to GABAergic, Dopaminergic and Glutamatergic signalling in the dorsal striatum of adult Male and Female mice with a conditional knockout of Bmal1 (ie: KO – knockout vs. WT- Wild Type) were evaluated at two different time points (ZT2 and ZT14) in order to determine the effect of a clock manipulation on the expression of DRD2, MAOA, A2a, GABBR1, and GAD67. The gene expression of these candidate targets was studied to gain a deeper understanding of the mechanism through which Bmal1 is linked to mood disorders and elucidate a clearer role on the influence of clock-controlled genes with relation to GABAergic, Glutamatergic, and Dopaminergic receptors. Evidence has suggested that disrupted clock function dysregulates cell signalling which contributes to the development of behavioral phenotypes associated with mood disorders. However, the etiology remains unclear. Therefore, this experiment allowed us to further examine the underlying molecular pathways associated with behavioral phenotypes observed in striatal-dependent clock gene knockout mice. Results indicated no significant differences in gene expression were observed in the candidates following gene deletion. Interestingly, different mis-regulation trends were observed in the targets, suggesting Bmal1 may play a role in the dysregulation of the candidates selected.