Adenosine and glutamate signaling in neuron-glial interactions: implications in alcoholism and sleep disorders.
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.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Hyung W
HW
Nam
Sally R
SR
McIver
David J
DJ
Hinton
Mahesh M
MM
Thakkar
Youssef
Y
Sari
Fiona E
FE
Parkinson
Phillip G
PG
Haydon
Doo-Sup
DS
Choi
D000241:Adenosine / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009457:Neuroglia / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D050600:SNARE Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012893:Sleep Wake Disorders / Q000378:metabolism* / Q000473:pathology
D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; C493397:SLC1A2 protein, human; D050600:SNARE Proteins; D018698:Glutamic Acid; D000241:Adenosine