The time course of adenosine, nitric oxide (NO) and inducible NO synthase changes in the brain with sleep loss and their role in the non-rapid eye movement sleep homeostatic cascade |
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Authors: | Kalinchuk Anna V McCarley Robert W Porkka-Heiskanen Tarja Basheer Radhika |
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Institution: | Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System and Harvard Medical School, West Roxbury, Massachusetts, USA. anna_kalinchuk@hms.harvard.edu |
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Abstract: | 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 sleep 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 non-rapid eye movement recovery sleep EEG delta power is known. Accordingly, we performed simultaneous hourly microdialysis sample collection from BF and frontal cortex (FC) during 11 h SD. We observed that both areas showed sequential increases in iNOS and NO, followed by increases in adenosine. BF increases began at 1 h SD, whereas FC increases began at 5 h 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. |
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Keywords: | adenosine cholinergic basal forebrain nitric oxide frontal cortex inducible nitric oxide synthase sleep homeostasis |
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