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

Abstract

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 increases extracellular adenosine levels, which regulates the ataxic and hypnotic/sedative (somnogenic) effects of ethanol. 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 ethanol 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.

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

“…Specifically, mice lacking ENT1 present with reduced adenosine levels in the nucleus accumbens (NAc). The reduction in adenosine levels caused by the deletion of ENT1 may be one of the possible molecular mechanisms underlying functional ethanol tolerance and dependence (Nam et al, 2012). In addition, ethanol drinking impairs several striatal functions including reward evaluation, motor function and habit formation.…”

Loss of Control of Alcohol Use and Severity of Alcohol Dependence in Non‐Treatment‐Seeking Heavy Drinkers Are Related to Lower Glutamate in Frontal White Matter

“…More general reduced WM integrity in multiple brain regions was found to be correlated with poorer performance on tasks of executive function (Brinkman et al, 2012). There is increasing evidence suggesting that many aspects of neuroplasticity associated with alcohol addiction involve changes in glutamatergic neurotransmission and glutamate (Glu) excitotoxicity (Nam et al, 2012). Not only in dependent but also nondependent alcohol consumption (Fitzgerald et al, 2012).…”

Zur Entstehung des Bewusstseins: Hypothese zur Rolle von Gliazellen, verzweigten Nervenenden und Dendritenarmen

“…Es gibt sogar ein Modell der Pathophysiologie der Depression, in dem eine stark erhöhte Expression von Rezeptoren in Astrozyten entscheidend ist [37,38], sowie Hypothesen zur möglichen Rolle von Gliazellen bezüglich der kognitiven Beeinträchtigungen bei der Schizophrenie [39,40,41], bei der Alzheimer-Demenz [42], bei der Epilepsie [43,44], beim Alkoholismus, bei Schlafstörungen [45] und bei neuropathischen Schmerzen [46,47]. …”