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The Journal of Neuroscience, July 15, 2000, 20(14):5544-5551

Granulocyte-Macrophage Colony-Stimulating Factor Modulates Rapid Eye Movement (REM) Sleep and Non-REM Sleep in Rats

Mayumi Kimura¹, Tohru Kodama², M. Cecilia Aguila³, Shi-Qing Zhang¹, and Shojiro Inoué¹

¹ Department of Biocybernetics, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan ² Department of Psychology, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183-8526, Japan, and ³ Department of Neurology, University of Miami, Miami, Florida 33125

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that may affect various functions of the CNS because the molecule and its receptors are expressed in the brain. The present study examines the effects of GM-CSF on sleep using rats and the secretion of three neurotransmitters/hormones that are involved in sleep regulation. When infused intracerebroventricularly at doses as low as 10 pmol for 10 hr during the dark period, GM-CSF promoted predominantly rapid eye movement (REM) sleep and moderate amounts of non-REM sleep without eliciting fever. An injection of GM-CSF (3.0 pmol) into the arcuate nucleus increased the release of nitric oxide (NO) from the hypothalamus but did not alter plasma levels of growth hormone. The release of somatostatin (SRIF) from the medial basal hypothalamus was stimulated by 1 × 10¹¹ M GM-CSF. These findings indicated that centrally administered GM-CSF stimulates SRIF release through activation of the NO system in the hypothalamus. Because SRIF promotes REM sleep, it may also mediate the effects of GM-CSF on REM sleep. The present study indicates a novel central effect of GM-CSF that modulates sleep, supporting the notion that hematopoietic cytokines also play roles in the CNS.

Key words: sleep; cytokine; hypothalamus; nitric oxide; somatostatin; rat

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20145544-08$05.00/0

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