Platelet glutamate uptake and Th1 cells inversely correlate in relapsing/remitting and in progressive multiple sclerosis

Abstract

Background: High affinity sodium-dependent Excitatory Amino Acid Transporters (EAAT), present in glial and neuron cells, clear around 90% of the synaptic cleft released glutamate, and their impaired activity seem to be critical for many neurodegenerative disorders, including Multiple Sclerosis (MS). These transporters are also present in human platelets, and they show molecular and biochemical characteristics similar to those in the CNS. Objectives: The aim of this study was to investigate whether EAAT-dependent uptake is present also at the peripheral level in blood of MS patients. Moreover, since platelets (plt) and peripheral blood mononuclear cells (PBMC) share the same intra-corporeal fluid, they might be reciprocally influenced, and the glutamate uptake modulation might be useful as a peripheral “trait-marker” to characterize different clinical courses of MS Results: Reduced uptake values were found in MS patients compared to healthy controls (HC), as well as significant differences were found across MS clinical courses. Representative saturation curves showed that Vmax was significantly decreased for patients compared to HC. Conversely, dissociation constant of the two reactions appeared similar for MS and HC subjects. Furthermore, clinical forms of MS with mild (benign) prognosis was not affected as fa as concern EAAT uptake. Gender, age, and drug treatments did not impact glutamate uptake efficiency. Interestingly, a negative correlation between EAAT activity and percentage of Th1 cells (CD4+IFNγ+ and CD4+TBET+IFNγ+ cells) was observed, suggesting a relationship between EAAT impairment and a pro-inflammatory environment. Conclusions: Interestingly, as shown in the CNS, a relationship between clinical, inflammatory MS features and glutamate clearance can be also assessed in platelets. Moreover, glutamate uptake activity might be an useful biomarker to characterize patients with benign prognosis.