Early chronotype and tissue-specific alterations of circadian clock function in spontaneously hypertensive rats.
Malfunction of the circadian timing system may result in cardiovascular and metabolic diseases, and conversely, these diseases can impair the circadian system. The aim of this study was to reveal whether the functional state of the circadian system of spontaneously hypertensive rats (SHR) differs from that of control Wistar rat. This study is the first to analyze the function of the circadian system of SHR in its complexity, i.e., of the central clock in the suprachiasmatic nuclei (SCN) as well as of the peripheral clocks. The functional properties of the SCN clock were estimated by behavioral output rhythm in locomotor activity and daily profiles of clock gene expression in the SCN determined by in situ hybridization. The function of the peripheral clocks was assessed by daily profiles of clock gene expression in the liver and colon by RT-PCR and in vitro using real time recording of Bmal1-dLuc reporter. The potential impact of the SHR phenotype on circadian control of the metabolic pathways was estimated by daily profiles of metabolism-relevant gene expression in the liver and colon. The results revealed that SHR exhibited an early chronotype, because the central SCN clock was phase advanced relative to light/dark cycle and the SCN driven output rhythm ran faster compared to Wistar rats. Moreover, the output rhythm was dampened. The SHR peripheral clock reacted to the dampened SCN output with tissue-specific consequences. In the colon of SHR the clock function was severely altered, whereas the differences are only marginal in the liver. These changes may likely result in a mutual desynchrony of circadian oscillators within the circadian system of SHR, thereby potentially contributing to metabolic pathology of the strain. The SHR may thus serve as a valuable model of human circadian disorders originating in poor synchrony of the circadian system with external light/dark regime.
Department of Neurohumoral Regulations, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
Martin
M
Sládek
Lenka
L
Polidarová
Marta
M
Nováková
Daniela
D
Parkanová
Alena
A
Sumová
D000818:Animals; D057906:Circadian Clocks; D003106:Colon / Q000378:metabolism / Q000503:physiopathology; D005347:Fibroblasts / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009928:Organ Specificity; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D013045:Species Specificity; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D059467:Transcriptome