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[Abstract Title]. - Society for Neuroscience

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Poster<br />

285. Sleep: Molecular, Cellular and Pharmacology I<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm<br />

Program#/Poster#: 285.8/QQ24<br />

Topic: E.08.c. Sleep: Molecular, cellular, and pharmacology<br />

Support: Grant-in-Aid <strong>for</strong> Scientific Research from the Japanese 21st Century COE Program,<br />

"Human Nutritional Science on Stress Control"<br />

<strong>Title</strong>: Bezafibrate, a PPARs agonist, enhances EEG delta oscillation during NREM sleep in mice<br />

Authors: *H. SEI 1 , S. CHIKAHISA 1 , K. TOMINAGA 2 , T. KAWAI 2 , K. OISHI 3 , N. ISHIDA 3 ,<br />

K. ROKUTAN 2 ;<br />

1 Dept Integrative Physiol., 2 Dept Stress Sci., Univ. Tokushima Grad. Sch., Tokushima, Japan;<br />

3 Clock Cell Biol. Res. Group, Natl. Inst. of Advanced Industrial Sci. and Technol., Tsukuba,<br />

Japan<br />

<strong>Abstract</strong>: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription<br />

factors belonging to the nuclear receptor family. We examined whether chronic treatment with<br />

bezafibrate, a PPARs pan agonist, would alter sleep and body temperature. Mice were fed with a<br />

control diet <strong>for</strong> two weeks, and body temperature, electroencephalogram and electromyogram<br />

were recorded <strong>for</strong> 48 hours, under light-dark conditions. After the baseline recording, the mice<br />

were provided with bezafibrate-supplemented food <strong>for</strong> two weeks, after which the same<br />

recordings were carried out. Two-week feeding of bezafibrate decreased body temperature<br />

especially during the latter half of the dark period. Body temperature rhythm and sleep/wake<br />

rhythm were phase-advanced about two to three hours by bezafibrate treatment. Bezafibrate<br />

treatment also increased the EEG delta power in non-rapid eye movement (NREM) sleep<br />

compared to the control diet throughout 24 hours. Furthermore, bezafibrate-treated mice showed<br />

no rebound of EEG delta power in NREM sleep after six hours of sleep deprivation. DNA<br />

microarray and real time RT-PCR analysis in the hypothalamus showed that bezafibrate<br />

treatment increased Neuropeptide Y mRNA and decreased pro-opiomelanocortin-alpha mRNA.<br />

These findings demonstrate that PPARs participate in the control of body temperature and sleep<br />

regulation, which accompanied with gene expression in the hypothalamus. Activation of PPARs<br />

may enhance deep sleep and improve resistance against sleep loss.<br />

Disclosures: H. Sei, None; S. Chikahisa, None; K. Tominaga, None; T. Kawai, None; K.<br />

Oishi, None; N. Ishida, None; K. Rokutan, None.

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