University of Kentucky

Cerebellar mRNA Levels of per 1, 2 as a Function of Sleep Deprivation in C57BL/6L Mice

Institution

University of Kentucky

Abstract

Circadian rhythms (driven by biological 24-hour internal clocks entrained by the lightdark cycle) and homeostatic mechanisms (an organism’s increasing sleep-drive with increasing sleep deprivation) both determine an organism’s level of sleepiness. The forebrain’s suprachiasmatic nucleus (SCN), a cluster of about 10,000 cells within the hypothalamus above the optic chiasm, houses mammals’ master circadian pacemaker. In mice, the SCN is known to oscillate in accordance with the expression of a small number of “clock-genes”: period genes per1 and per2 (per1,2); cryptochrome genes cry1 and cry2 (cry1,2); and transcriptional regulators clock and bmal1. Data implicates cry1,2 and per1,2 in participation in both circadian and homeostatic aspects of sleep in mice. In mouse cerebellar granule cells, induction pathways for per1 mRNA expression have been identified, and physiological roles of per1,2 mRNA expression have been explored through anxiolytic drugs. Still, per1,2 mRNA expression’s function in the cerebellum remains unclear. The role(s) of cerebellar per1,2 mRNA expression in sleep regulation are explored using Real-Time Polymerase Chain Reaction quantification by testing the following hypotheses: 1) per1,2 mRNA levels in the cerebellum have a positive correlation with increasing amounts of sleep deprivation (SD), 2) mice allowed some sleep recovery time following SD have decreased per1,2 mRNA levels in the Cerebellum, and 3) Knockout mice with abnormalities in sleep homeostasis have corresponding alterations in per1,2 mRNA levels.

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Cerebellar mRNA Levels of per 1, 2 as a Function of Sleep Deprivation in C57BL/6L Mice

Circadian rhythms (driven by biological 24-hour internal clocks entrained by the lightdark cycle) and homeostatic mechanisms (an organism’s increasing sleep-drive with increasing sleep deprivation) both determine an organism’s level of sleepiness. The forebrain’s suprachiasmatic nucleus (SCN), a cluster of about 10,000 cells within the hypothalamus above the optic chiasm, houses mammals’ master circadian pacemaker. In mice, the SCN is known to oscillate in accordance with the expression of a small number of “clock-genes”: period genes per1 and per2 (per1,2); cryptochrome genes cry1 and cry2 (cry1,2); and transcriptional regulators clock and bmal1. Data implicates cry1,2 and per1,2 in participation in both circadian and homeostatic aspects of sleep in mice. In mouse cerebellar granule cells, induction pathways for per1 mRNA expression have been identified, and physiological roles of per1,2 mRNA expression have been explored through anxiolytic drugs. Still, per1,2 mRNA expression’s function in the cerebellum remains unclear. The role(s) of cerebellar per1,2 mRNA expression in sleep regulation are explored using Real-Time Polymerase Chain Reaction quantification by testing the following hypotheses: 1) per1,2 mRNA levels in the cerebellum have a positive correlation with increasing amounts of sleep deprivation (SD), 2) mice allowed some sleep recovery time following SD have decreased per1,2 mRNA levels in the Cerebellum, and 3) Knockout mice with abnormalities in sleep homeostasis have corresponding alterations in per1,2 mRNA levels.