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Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol.
Neuropharmacology. 2016 08; 107:181-188.N

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, University of the Sciences, Philadelphia College of Pharmacy, Philadelphia, PA 19104, USA. Electronic address: a.suryanarayanan@usciences.edu.Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY 13902, USA.Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY 13902, USA.Departments of Psychiatry and Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY 13902, USA.Division of Oral Biology & Medicine, School of Dentistry, 63-078 CHS, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: igor@ucla.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27016017

Citation

Suryanarayanan, A, et al. "Role of Interleukin-10 (IL-10) in Regulation of GABAergic Transmission and Acute Response to Ethanol." Neuropharmacology, vol. 107, 2016, pp. 181-188.
Suryanarayanan A, Carter JM, Landin JD, et al. Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol. Neuropharmacology. 2016;107:181-188.
Suryanarayanan, A., Carter, J. M., Landin, J. D., Morrow, A. L., Werner, D. F., & Spigelman, I. (2016). Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol. Neuropharmacology, 107, 181-188. https://doi.org/10.1016/j.neuropharm.2016.03.027
Suryanarayanan A, et al. Role of Interleukin-10 (IL-10) in Regulation of GABAergic Transmission and Acute Response to Ethanol. Neuropharmacology. 2016;107:181-188. PubMed PMID: 27016017.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol. AU - Suryanarayanan,A, AU - Carter,J M, AU - Landin,J D, AU - Morrow,A L, AU - Werner,D F, AU - Spigelman,I, Y1 - 2016/03/22/ PY - 2016/01/22/received PY - 2016/03/08/revised PY - 2016/03/21/accepted PY - 2016/3/27/entrez PY - 2016/3/27/pubmed PY - 2017/6/22/medline KW - Alcohol KW - Anti-inflammatory KW - GABAA KW - Interleukin-10 KW - Neuroimmune KW - mIPSC SP - 181 EP - 188 JF - Neuropharmacology JO - Neuropharmacology VL - 107 N2 - 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. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/27016017/Role_of_interleukin_10__IL_10__in_regulation_of_GABAergic_transmission_and_acute_response_to_ethanol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(16)30099-5 DB - PRIME DP - Unbound Medicine ER -