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

• 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: Oxford, UK Blackwell Publishing Ltd 01-01-2011; Wiley-Blackwell
• Subjects: Adenosine; Adenosine - metabolism; Adenosine - physiology; Ageing, cell death; Animals; Biochemistry and metabolism; Biological and medical sciences; Brain; Cell physiology; Central nervous system; Cerebral Cortex - metabolism; Cerebral Cortex - physiology; cholinergic basal forebrain; Cortex (frontal); Data processing; EEG; Electroencephalography - methods; Forebrain (basal); frontal cortex; Fundamental and applied biological sciences. Psychology; Homeostasis; Homeostasis - physiology; inducible nitric oxide synthase; Male; Microdialysis; Molecular and cellular biology; Neurochemistry; Neurons; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide - physiology; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type II - physiology; Nitric-oxide synthase; Prosencephalon - metabolism; Prosencephalon - physiology; Rats; Rats, Wistar; Sleep (NREM); Sleep and wakefulness; Sleep deprivation; Sleep Deprivation - metabolism; sleep homeostasis; Sleep Stages - physiology; Time Factors; Vertebrates: nervous system and sense organs; Adenosine; Deprivation; cholinergic basal forebrain; Enzyme; Central nervous system; Electrophysiology; Homeostasis; sleep homeostasis; Electroencephalography; Rapid eye movement sleep; Extracellular; Nitric-oxide synthase; Site of action; Encephalon; inducible nitric oxide synthase; frontal cortex; Wakefulness; Nitric oxide; Sleep wake cycle; Oxidoreductases; Release
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.07100.x

J. Neurochem. (2011) 116, 260–272.
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.