Effect of the cytokine Interleukin 6 on Acid sensing ion channel (ASIC1) distribution in hippocampal neurons.

GONZÁLEZ, CARLOTA; WEISSMANN; UCHITEL, OSVALDO DANIEL; SALINAS, LIBIA CATALINA

Washington

Congreso; neuroscience 2017; 2017

Society of neuroscience

Neuroinflammation has long been analyzed as a contributor to neurodegenerative processes. The inflammation hypothesis proposes that chronic inflammatory response is a crucial factor in the onset and progression of neurodegeneration.Cytokines are essential modulators of the immune response; and Interleukin 6 (IL-6) is one of the main neuroinflammatory cytokines in the central nervous system (CNS). Both glial and neuronal cells express IL-6 and IL-6R (receptor) in the brain. CNS IL-6 is upregulated when neuroinflammation occurs, and IL-6 levels are increased in sera of Parkinson´s, Huntington´s as well as in animal models of these diseases. In addition, inflammation determines changes in metabolic activity and can result in acidosis. Changes in regional pH levels in the brain have been observed in a number of neurological and neurodegenerative disorders. ASIC (Acid sensing Ion) channels are sodium channels activated by tissue acidosis and thus become active in many pathological conditions. ASIC1 is the most abundant ASIC subunit in the mammalian central nervous system. Physiologically, its activation is related to synaptic plasticity, learning and memory. ASIC1 channels in particular permeate not only sodium but slightly calcium ions, and so can contribute to intracellular calcium levels and neuronal injury in pathological conditions. In fact, ASIC1 channels have been lately implicated in several neurological diseases, as blocking this channel with ASIC1 toxin improves models of cerebral ischemia, Parkinson´s disease, Huntington´s and ALS. Therefore, we decided to analyze the role of IL-6 on ASIC1 channels. We studied dissociated mouse hippocampal cultures after 8-12 DIV (days in vitro). We incubated the cultures with IL-6 (10 ng/ml 30 minutes) and did immunocytochemistry of the samples to detect ASIC1. In parallel we studied the ASIC currents elicited by applying a puf of saline at pH 6.1 under whole cell patch-clamp conditions. Our preliminary results show that IL-6 determines the redistribution of a cytosolic pool of ASIC1 channels to the membrane of the neurons, which correlates with an increase in ASIC1 currents amplitude. These results point at a mechanism by which neuroinflammation could contribute to neurodegeneration; and ASIC1as a potential target to aim at in these conditions.