1. Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol
- Author
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Suryanarayanan, A, Carter, JM, Landin, JD, Morrow, AL, Werner, DF, and Spigelman, I
- Subjects
Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Alcoholism ,Alcohol Use and Health ,Substance Misuse ,Neurosciences ,Good Health and Well Being ,Animals ,Binge Drinking ,Brain ,Cells ,Cultured ,Central Nervous System Depressants ,Disease Models ,Animal ,Dose-Response Relationship ,Drug ,Ethanol ,Hypnotics and Sedatives ,Inhibitory Postsynaptic Potentials ,Interleukin-10 ,Male ,Miniature Postsynaptic Potentials ,Neurons ,Phosphatidylinositol 3-Kinases ,Phosphoinositide-3 Kinase Inhibitors ,Rats ,Sprague-Dawley ,Receptors ,GABA-A ,Sleep ,Synaptic Transmission ,Tissue Culture Techniques ,gamma-Aminobutyric Acid ,Alcohol ,GABAA ,Neuroimmune ,Anti-inflammatory ,mIPSC ,Neurology & Neurosurgery ,Pharmacology and pharmaceutical sciences ,Biological psychology - Abstract
Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (Itonic), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and Itonic, but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered.
- Published
- 2016