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Interferon-gamma potentiates GABA(A) receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Birnir: Molecular Physiology and Neuroscience. (louise.flood@neuro.uu.se)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Birnir: Molecular Physiology and Neuroscience.ORCID iD: 0000-0001-8279-2790
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry. Uppsala Univ, Uppsala Univ Hosp, Dept Neurosci, Psychiat, Uppsala, Sweden.ORCID iD: 0000-0002-5760-7730
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Birnir: Molecular Physiology and Neuroscience.ORCID iD: 0000-0002-1763-0266
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2019 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 337, article id UNSP 577050Article in journal (Refereed) Published
Abstract [en]

The neural transmission and plasticity can be differentially modulated by various elements of the immune system. Interferon-gamma (IFN-gamma) is a "pro-inflammatory" cytokine mainly produced by T lymphocytes, activates its corresponding receptor and plays important roles under both homeostatic and inflammatory conditions. However, the impact of IFN-gamma on the gamma-aminobutyric acid (GABA)-mediated currents in the hippocampus, a major brain region involved in the cognitive function, has not been investigated. Here we detected abundant expression of both IFN-gamma receptor subunit gene transcripts (Ifngrl and Ifngr2) in the rat hippocampus by quantitative PCR. In addition, we pre-incubated rat hippocampal slices with IFN-gamma (100 ng/ml) and recorded GABA-activated spontaneous and miniature postsynaptic inhibitory currents (sIPSCs and mIPSCs) and tonic currents in hippocampal CAl pyramidal neurons by the whole-cell patch-clamp method. The pre-incubation with IFN-gamma increased the frequency but not the mean amplitude, rise time or decay time of both sIPSCs and mIPSCs in hippocampal CAl pyramidal neurons, suggesting a presynaptic effect of IFN-gamma. Moreover, the GABA-activated tonic currents were enhanced by IFN-gamma. In conclusion, the potentiation of GABAergic currents in hippocampal neurons by IFN-gamma may contribute to the disturbed neuronal excitability and cognitive dysfunction during neuroinflammation.

Place, publisher, year, edition, pages
ELSEVIER , 2019. Vol. 337, article id UNSP 577050
Keywords [en]
gamma-Aminobutyric acid, Hippocampus, Interferon-gamma, Phasic inhibition, Tonic inhibition
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-400001DOI: 10.1016/j.jneuroim.2019.577050ISI: 000498318800004PubMedID: 31505410OAI: oai:DiVA.org:uu-400001DiVA, id: diva2:1380791
Funder
Swedish Research Council, Dnr 201502417Swedish Research Council, 2018-02952The Swedish Brain FoundationAvailable from: 2019-12-19 Created: 2019-12-19 Last updated: 2019-12-19Bibliographically approved

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Flood, LouiseKorol, SergiyEkselius, LisaBirnir, BryndisJin, Zhe
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