Circadian Oscillations of Molecular Clock Components in the Cerebellar Cortex of the Rat

Abstract

The central circadian clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the circadian clockwork of the SCN constitutes a self-sustained autoregulatory feedback mechanism reflected by the rhythmic expression of clock genes. However, recent studies have shown the presence of extrahypothalamic oscillators in other areas of the brain including the cerebellum. In the present study, the authors unravel the cerebellar molecular clock by analyzing clock gene expression in the cerebellum of the rat by use of radiochemical in situ hybridization and quantitative real-time polymerase chain reaction. The authors here show that all core clock genes, i.e., Per1, Per2, Per3, Cry1, Cry2, Clock, Arntl, and Nr1d1, as well as the clock-controlled gene Dbp, are expressed in the granular and Purkinje cell layers of the cerebellar cortex. Among these genes, Per1, Per2, Per3, Cry1, Arntl, Nr1d1, and Dbp were found to exhibit circadian rhythms in a sequential temporal manner similar to that of the SCN, but with several hours of delay. The results of lesion studies indicate that the molecular oscillatory profiles of Per1, Per2, and Cry1 in the cerebellum are controlled, though possibly indirectly, by the central clock of the SCN. These data support the presence of a circadian oscillator in the cortex of the rat cerebellum. (Author correspondence: [email protected])

Keywords:

• Cerebellum
• Circadian clock
• Clock gene
• Extrahypothalamic oscillator
• Suprachiasmatic nucleus

ACKNOWLEDGMENTS

The authors wish to thank Ms. Tine Thorup Mellergaard for expert technical assistance.

Declaration of Interest: This study was supported by the Danish Medical Research Council (grant number 271-09-0206), the Lundbeck Foundation (grant number R34-A3364), the Novo Nordisk Foundation (grant number 27-11-08), and the Carlsberg Foundation (grant number 2008-01-0063).

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.