Abnormal activity of the Na/Ca exchanger enhances glutamate transmission in experimental autoimmune encephalomyelitis

Brain, Behavior, and Immunity
Silvia RossiDiego Centonze

Abstract

It is increasingly accepted that excessive glutamate release plays a key role in the pathophysiology of grey matter damage in multiple sclerosis (MS). The mechanisms causing abnormal glutamate transmission in this disorder are however largely unexplored. By means of electrophysiological recordings from single striatal neurons in slices, we found that the presymptomatic and acute phases of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS, are associated with enhanced synaptic release of glutamate. The reverse mode of action of axonal Na(+)/Ca(++) exchanger, secondary to abnormal functioning of voltage-dependent Na(+) channels, was identified as a major cause of this alteration. In fact, inhibition of the Na(+)/Ca(++) exchanger with bepridil or with KB-R7943, which selectively blocks the reverse mode of the exchanger, reduced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from striatal neurons in EAE mice but not in control animals. In the presence of tetrodotoxin (TTX), a blocker of voltage-dependent Na(+) channels, the effect of bepridil was normalized in acute (25 days post-immunization) EAE mice, indicating that axonal accumulation of Na(+) ions flowing through voltag...Continue Reading

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Citations

Mar 23, 2013·Brain : a Journal of Neurology·Valérie JolivelAri Waisman
Jul 31, 2013·Neuromolecular Medicine·Francesco MoriDiego Centonze
Apr 15, 2014·Neuroscience and Biobehavioral Reviews·Sagit WeissDiego Centonze
Aug 29, 2012·British Journal of Pharmacology·G GrasselliD Centonze
Apr 9, 2011·Brain, Behavior, and Immunity·Silvia RossiDiego Centonze
Dec 10, 2013·International Immunopharmacology·Stefan H P KrausValérie Jolivel
Sep 21, 2013·Journal of Neuroimmunology·Alessandra MusellaDiego Centonze
Jun 17, 2011·Multiple Sclerosis : Clinical and Laboratory Research·S RossiD Centonze
Oct 19, 2012·Multiple Sclerosis : Clinical and Laboratory Research·Arun V Krishnan, Matthew C Kiernan
Dec 13, 2012·Multiple Sclerosis : Clinical and Laboratory Research·Francesca RuffiniGianvito Martino
Nov 21, 2015·Nature Reviews. Neurology·Georgia MandolesiDiego Centonze

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