Adenosine and Glutamate Signaling in Neuron-Glial Interactions: Implications in Alcoholism and Sleep Disorders

• Published in: Alcoholism, clinical and experimental research Vol. 36; no. 7; pp. 1117 - 1125
• Main Authors: Nam, Hyung W., McIver, Sally R., Hinton, David J., Thakkar, Mahesh M., Sari, Youssef, Parkinson, Fiona E., Haydon, Phillip G., Choi, Doo-Sup
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Blackwell Publishing Ltd 01.07.2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Addictive behaviors; Adenosine; Adenosine - metabolism; Adult and adolescent clinical studies; Alcoholism; Alcoholism - metabolism; Alcoholism - pathology; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Cell Communication - physiology; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; Glutamate; Glutamate Plasma Membrane Transport Proteins - metabolism; Glutamic Acid - metabolism; Humans; Medical sciences; Nervous system (semeiology, syndromes); Neuroglia - metabolism; Neuroglia - physiology; Neurology; Neurons - metabolism; Neurons - physiology; Pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Signal Transduction - physiology; Signaling; Sleep; Sleep Wake Disorders - metabolism; Sleep Wake Disorders - pathology; SNARE Proteins - metabolism; Toxicology; Nervous system diseases; Purine nucleoside; Adenosine; Glial cell; Neuroglia; Alcoholism; Interaction; Sleep disorder; Pharmacology; Glutamate; Signal transduction; Signaling; Neuron; Sleep; Excitatory aminoacid; Neurotransmitter; Sleep wake cycle; Neurological disorder
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2011.01722.x

Recent studies have demonstrated that the function of glia is not restricted to the support of neuronal function. Especially, astrocytes are essential for neuronal activity in the brain. Astrocytes actively participate in synapse formation and brain information processing by releasing or uptaking gliotransmitters such as glutamate, d‐serine, adenosine 5′‐triphosphate (ATP), and adenosine. In the central nervous system, adenosine plays an important role in regulating neuronal activity as well as in controlling other neurotransmitter systems such as GABA, glutamate, and dopamine. Ethanol (EtOH) increases extracellular adenosine levels, which regulates the ataxic and hypnotic/sedative (somnogenic) effects of EtOH. Adenosine signaling is also involved in the homeostasis of major inhibitory/excitatory neurotransmission (i.e., GABA or glutamate) through neuron–glial interactions, which regulates the effect of EtOH and sleep. Adenosine transporters or astrocytic SNARE‐mediated transmitter release regulates extracellular or synaptic adenosine levels. Adenosine then exerts its function through several adenosine receptors and regulates glutamate levels in the brain. This review presents novel findings on how neuron–glial interactions, particularly adenosinergic signaling and glutamate uptake activity involving glutamate transporter 1 (GLT1), are implicated in alcoholism and sleep disorders.