Oxidative stress and glutamate uptake impairment in Multiple Sclerosis: any possible relationship?

Glutamate-uptake (GLU-up) impairment and an associated excitotoxic neuronal damage are widely documented in neurodegenerative diseases, as Multiple Sclerosis (MS) can be considered. Several factors negatively affect GLU-up, among them is the oxidative stress (OXS). Considering the suggested involvement of both GLU-up and OXS in neurodegenerative mechanisms of MS, we investigated a possible relationship between these factors. Fifty MS patients (age 33–64 years) with different disease course and 55 controls (HC, age 33–60 years) were studied for several serum markers of OXS and antioxidant factors, namely: coenzyme-Q10, total, oxidized and reduced forms of glutathione, malondialdehyde, reactive-oxygen-species, anti-oxidized-low-density lipoproteins antibodies (Anti-oxLDL), and anti-oxidant-power. Activity and affinity of glutamate platelet transporters were also studied. Coenzyme-Q10 and malondialdehyde were determined by an isocratic HPLC with UV detection, glutathione by HPLC with fluorescence detection, reactive-oxygen-species were photometrically quantified, anti-oxLDL were detected by ELISA, anti-oxidant-power was measured by the Cu++ reduction, subsequently detected by a chromogenic reaction. Sodium/energy-dependent-glutamate-uptake was studied in platelets measuring tritiated-Glu by b-counter and normalized to proteins’ amount. Reduced GLU-up values was found in MS compared to HC (19 ± 1.8; 28 ± 2.4 pmoles/mg prot/30 min ± SEM; p B 0.003), even if in benign MS subgroup no uptake decrease was observed. Coenzyme-Q10, one of the most powerful antioxidant was lower in MS (517 ± 35.7 lg/L) compared to HC (626 ± 27.7 lg/L p.02). While oxidated- glutathione levels were higher in SM (62 ± 3.7 U/ml) versus HC (48 ± 4.3U/ml, p = 0.01). A trend for higher antioxLDL in MS patients (35 ± 2.5 U/ml) versus HC (31 ± 4.7 U/ml) was found as well. We described a reduced GLU-up activity in MS patients compared to HC; Vm was significantly decreased (p.003), whereas Km was unaffected. Hence, we might suggest that the uptake impairment is associated to a reduced GLU- transporter expression or to a structural damage. OXS maybe one of the mechanisms involved in both these processes. Interestingly, we found a higher antioxidant ‘‘protection’’ in benign MS, where GLU-up was increased versus RR and SP SM (p.05). Correlation analyses between all OXS markers measured and GLU-up as well as across different courses of MS patients will be discussed