Circadian rhythms of clock gene expression in the cerebellum of serotonin-deficient Pet-1 knockout mice

Abstract

Serotonin plays an important role in the central regulation of circadian clock function. Serotonin levels are generally higher in the brain during periods of high activity, and these periods are in turn heavily regulated by the circadian clock located in the suprachiasmatic nucleus. However, the role of serotonin as a regulator of circadian rhythms elsewhere in the brain has not been extensively examined. In this study, we examined circadian rhythms of clock gene expression in the cerebellum in mice lacking the Pet-1 transcription factor, which results in a developed brain that is deficient in serotonin neurons. If serotonin helps to synchronize rhythms in brain regions other than the suprachiasmatic nucleus, we would expect to see differences in clock gene expression in these serotonin deficient mice. We found minor differences in the expression of Per1 and Per2 in the knockout mice as compared to wild type, but these differences were small and of questionable functional importance. We also measured the response of cerebellar clocks to injections of the serotonin agonist 8-OH-DPAT during the early part of the night. No effect on clock genes was observed, though the immediate-early gene Fos showed increased expression in wild type mice but not the knockouts. These results suggest that serotonin is not an important mediator of circadian rhythms in the cerebellum in a way that parallels its regulation of the circadian clock in the suprachiasmatic nucleus.

Circadian Clock Proteins and Melatonin Receptors in Neurons and Glia of the Sapajus apella Cerebellum

“…The cerebellum participates in the behavior of anticipating the time of food accessibility, which involves increased activity, behavioral arousal, and body temperature changes (Mistlberger, 1994 ; Mendoza et al, 2010 ). Thereby, the present study expands current knowledge on the rhythmic characteristics of the cerebellum, which was previously based on investigations showing clock gene expression in rodent and human studies (Shieh, 2003 ; Farnell et al, 2008 ; Mendoza et al, 2010 ; Rath et al, 2012 ; Li et al, 2013 ; Paulus and Mintz, 2016 ). These rhythmic clock gene and protein expressions are transduced into a rhythmic neuronal output signal that can influence other brain targets and play a crucial role in the anticipation of 24 h predictable environmental changes (Courtemanche et al, 2013 ).…”

“…The molecular basis of the cerebellar oscillator has been demonstrated by clock gene expression in the cerebellar cortex of rodents (Shieh, 2003 ; Mendoza et al, 2010 ; Rath et al, 2012 ; Paulus and Mintz, 2016 ). Some clock genes, i.e., Per1, Per2, Per3, Arntl, Cry1, Nr1d1 , and Dbp , are rhythmically expressed (Takumi et al, 1998 ; Rath et al, 2012 ) while others, i.e., Cry2 and Clock , are constitutively expressed (Guilding and Piggins, 2007 ; Rath et al, 2012 ).…”

The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders

“…Serotonin travels from the source to target cells (neurons and astroglia) through energy gradients, leading to its diffusion and convection [ 134 ]. By interacting with its receptors, 5-HT is responsible for the regulation of many processes important for life, which include perception, mood, anxiety, aggression, cognitive functions, attention, sexual functions, and the circadian rhythm [ 131 , 135 , 136 ].…”