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This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/R197    most recent 00828.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Imeri, L. Articles by Opp, M. R. Search for Related Content PubMed PubMed Citation Articles by Imeri, L. Articles by Opp, M. R.

SLEEP AND TEMPERATURE REGULATION

Inhibition of caspase-1 in rat brain reduces spontaneous nonrapid eye movement sleep and nonrapid eye movement sleep enhancement induced by lipopolysaccharide

¹Institute of Human Physiology II, and ²Giuseppe Moruzzi Centre for Experimental Sleep Research, University of Milan Medical School, Milan, Italy; Departments of ³Anesthesiology and ⁴Molecular and Integrative Physiology, and the ⁵Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, Michigan

Submitted 28 November 2005 ; accepted in final form 30 January 2006

Evidence suggests that IL-1 is involved in promoting physiological nonrapid eye movement (NREM) sleep. IL-1 has also been proposed to mediate NREM sleep enhancement induced by bacteria or their components. Mature and biologically active IL-1 is cleaved from an inactive precursor by a cysteinyl aspartate-specific protease (caspase)-1. This study aimed to test the hypothesis that inhibition in brain of the cleavage of biologically active IL-1 will reduce in rats both spontaneous NREM sleep and NREM sleep enhancement induced by the peripheral administration of components of the bacterial cell wall. To test this hypothesis, rats were intracerebroventricularly administered the caspase-1 inhibitor Ac-Tyr-Val-Ala-Asp chloromethyl ketone (YVAD; 3, 30, 300, and 1,500 ng) or were pretreated intracerebroventricularly with YVAD (300 ng) and then intraperitoneally injected with the gram-negative bacterial cell wall component LPS (250 µg/kg). Subsequent sleep-wake behavior was determined by standard polygraphic recordings. YVAD administration at the beginning of the light phase of the light-dark cycle significantly reduced time spontaneously spent in NREM sleep during the first 12 postinjection hours. YVAD pretreatment also completely prevented NREM sleep enhancement induced by peripheral LPS administration at the beginning of the dark phase. These results, in agreement with previous evidence, support the involvement of brain IL-1 in physiological promotion of NREM sleep and in mediating NREM sleep enhancement induced by peripheral immune challenge.

interleukin-1 converting enzyme; caspase inhibitors; cytokine