THE TIME COURSE OF ADENOSINE, NITRIC OXIDE (NO) AND INDUCIBLE NO SYNTHASE CHANGES IN THE BRAIN WITH SLEEP LOSS AND THEIR ROLE IN THE NREM SLEEP HOMEOSTATIC CASCADE

• Published in: Journal of neurochemistry Vol. 116; no. 2; pp. 260 - 272
• Main Authors: Kalinchuk, Anna V., McCarley, Robert W., Porkka-Heiskanen, Tarja, Basheer, Radhika
• Format: Journal Article
• Language: English
• Published: 02-12-2010
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.07100.x

Both adenosine and nitric oxide (NO) are known for their role in sleep homeostasis, with the basal forebrain (BF) wakefulness center as an important site of action. Previously we reported a cascade of homeostatic events, wherein sleep deprivation (SD) induces the production of inducible nitric oxide synthase (iNOS)-dependent NO in BF, leading to enhanced release of extracellular adenosine. In turn, increased BF adenosine leads to enhanced sleep intensity, as measured by increased non-rapid eye movement (NREM) EEG delta activity. However, the presence and time course of similar events in cortex has not been studied, although a frontal cortical role for the increase in NREM recovery sleep EEG delta power is known. Accordingly, we performed simultaneous hourly microdialysis sample collection from BF and frontal cortex (FC) during 11h SD. We observed that both areas showed sequential increases in iNOS and NO, followed by increases in adenosine. BF increases began at 1h SD, while FC increases began at 5h SD. iNOS and Fos-double labeling indicated that iNOS induction occurred in BF and FC wake-active neurons. These data support the role of BF adenosine and NO in sleep homeostasis and indicate the temporal and spatial sequence of sleep homeostatic cascade for NO and adenosine.