Lack of TNFRp55 modifies circadian rhythms of locomotor activity and clock genes expression in the liver

RAGUSA JA; DE LA VEGA M; CASAIS M; ANZULOVICH AC

Congreso; Sociedad de Biología de Cuyo XXXI Reunión Científica Anual; 2013

LACK OF TNFRp55 MODIFIES CIRCADIAN RHYTHMS OF LOCOMOTOR ACTIVITY AND CLOCK GENES EXPRESSION IN THE LIVER. Ragusa JA, De la Vega M, Casais M and Anzulovich AC. IMIBIO-SL, CONICET-UNSL, San Luis. E-mail: acanzu@unsl.edu.ar Circadian rhythms in peripheral clocks, such as the liver, are controlled by neuroimmunendocrine signals proceeding from the master clock in the suprachiasmatic nucleus and locally regulated by the cellular clock transcription factors. TNFα is a pleiotropic cytokine which binds to cognate membrane receptors TNFRp55 and TNFRp75. Our objective was to evaluate the consequences of TNFRp55 deficiency on the 24h locomotor activity pattern, a function controlled by the master clock in the SCN, as well as on the circadian profiles of three key clock factors, Clock, Per1 and Cry1, in the liver of female mice in diestrous. Locomotor activity was recorded using a computational adquisition data system equipped with infrared detectors. Circadian clock genes expression was determined by RT-PCR from liver samples obtained every 6 hours from female mice maintained under constant darkness during 7 days before the experiment.As expected, Clock, Per1 and Cry1 expression is circadian and endogenously driven in the mouse liver. Lack of TNFRp55 decreases locomotor activity of female mice and modifies clock genes circadian rhythms in the liver. Particularly, it abolished Cry1 rhythmicity and advanced Clock and Per1 rhythms? phases. Thus, we suggest TNFα, through its p55 receptor signaling pathway, could play a role in the temporal organization of the circadian clock in the liver, a peripheral clock with relevant function in metabolism.