Cytokine inflammatory threat, but not LPS one, shortens GABAergic synaptic currents in the mouse spinal cord organotypic cultures

Journal of Neuroinflammation

  ^{1    2    2    3    4    4    5} 

[1] 0000 0001 1941 4308, grid.5133.4, Department of Life Sciences, University of Trieste, 34127, Trieste, Italy;0000 0004 1757 2304, grid.8404.8, Department NEUROFARBA, University of Florence, 50139, Florence, Italy;0000 0004 1757 2304, grid.8404.8, Dipartimento di Medicina Sperimentale e Clinica, University of Florence, 50139, Florence, Italy;0000 0004 1762 9868, grid.5970.b, International School for Advanced Studies (SISSA/ISAS), 34136, Trieste, Italy;0000 0004 1762 9868, grid.5970.b, International School for Advanced Studies (SISSA/ISAS), 34136, Trieste, Italy;0000 0001 2322 6764, grid.13097.3c, Present address: Wolfson Centre for Age Related Disease, King’s College London, Guy’s Campus, SE1 1UL, London, UK;

关键词: Organotypic spinal slices;    Patch-clamp;    Synaptic currents;    Neuroinflammation;    GABAergic inhibition;    GABAergic receptors;    Spinal circuits;    NKCC1;    Resident neuroglia;   

DOI  :  10.1186/s12974-019-1519-z

来源: publisher

【 摘 要 】

BackgroundSynaptic dysfunction, named synaptopathy, due to inflammatory status of the central nervous system (CNS) is a recognized factor potentially underlying both motor and cognitive dysfunctions in neurodegenerative diseases. To gain knowledge on the mechanistic interplay between local inflammation and synapse changes, we compared two diverse inflammatory paradigms, a cytokine cocktail (CKs; IL-1β, TNF-α, and GM-CSF) and LPS, and their ability to tune GABAergic current duration in spinal cord cultured circuits.MethodsWe exploit spinal organotypic cultures, single-cell electrophysiology, immunocytochemistry, and confocal microscopy to explore synaptic currents and resident neuroglia reactivity upon CK or LPS incubation.ResultsLocal inflammation in slice cultures induced by CK or LPS stimulations boosts network activity; however, only CKs specifically reduced GABAergic current duration. We pharmacologically investigated the contribution of GABAAR α-subunits and suggested that a switch of GABAAR α1-subunit might have induced faster GABAAR decay time, weakening the inhibitory transmission.ConclusionsLower GABAergic current duration could contribute to providing an aberrant excitatory transmission critical for pre-motor circuit tasks and represent a specific feature of a CK cocktail able to mimic an inflammatory reaction that spreads in the CNS. Our results describe a selective mechanism that could be triggered during specific inflammatory stress.

【 授权许可】

CC BY