Glutamatergic Homeostasis Impairment in Multiple Sclerosis Patients

Background: Background There is huge body of evidences concerning the detrimental role of glutamate excess in Multiple Sclerosis (MS). Excessive neuronal stimulation, due to deficient removal of glutamate and\or excessive release by activated Tcell and microglia, may trigger an enzymatic cascade leading to cell death. For MS, however, is still not cleared-up whether this imbalance relies to a glutamate overproduction or to its reduced clearance. Our group previously reported an impairment of glutamate transporter (EAAT) in neurodegenerative diseases at platelets (P) level, mirroring that present at central nervous system. Design/Methods: Design/Methods: We investigated P-EAAT activity as Glutamate-uptake marker, in primary progressive (PP=17), secondary (SP=16), relapsing remitting (RR=25) and benign (BB=12) MS population (=70) and 60 Healthy controls (HC). Sodium/energy-dependent-glutamate-uptake was studied in platelets measuring tritiated-Glu by beta-counter, following the original method of Mangano and Schwarcz, and activity and affinity were expressed by Vm and Km. Results: Results: Reduced glutamate-uptake values were found in MS compared to controls (18,23 1.82; 26.26 2.03 pmoles/mg prot/30min S.E.; p=0.03). Statistical analysis by one-way ANOVA showed p<0.0001 among the different group of patients compared to HC and BB-MS (36.45 6.64). Vm was significantly decreased (HC= 218, MS=56), whereas Km(HC=53, MS=48.5) was unaffected. Conclusions: Conclusions: Hence, we might suggest that the uptake impairment is not due to a reduced affinity of EAAT for glutamate but maybe due to a reduced EAAT activity. This could occur because of a structural damage and/or interference with other environmental molecules, rather than a reduced protein expression. The finding of an almost unaffected EAAT activity in BB-MS might suggest a different involvement of glutammatergic-excitotossicity along with the different course of MS.