Modulation of neurological deficits during EAE by glutamate receptors antagonists MPEP and amantadine

• Autorzy: Sulkowski G. , Dabrowska-Bouta B. , Lenkiewicz A. , Struzynska L.
• Języki publikacji: EN

Abstrakty

EN

Chronic glutamate-mediated excitotoxicity has been suggested to contribute to the pathogenesis of Multiple Sclerosis (MS). Recent data suggest that inhibition of glutamate neurotransmission via specific interaction with glutamate receptors (GluRs) might be interesting for inhibition of disease progression and early symptomatic treatment in MS. The aim of our investigation was to study the role of NMDA receptors and group I mGluRs in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We tested the effect of MPEP (2-methyl-6-(phenylethynyl)-pyridine), the mGluR5 antagonist, in dose of 5 mg/kg b.w./day, and amantadine (the uncompetitive NMDA receptor antagonist) in dose of 100 mg/kg b.w./day on development of neurological deficits in EAE rats. Both drugs were administered intraperitoneally ones daily into EAE rats during 7 days, starting from day 5 to 12 post immunization. The neurological symptoms of EAE started at 10-11 days post immunization and peaked after 12-13 days. We noted the changes in body weight during the course of EAE. Until day 8 p.i. the body weight of rats in control and treated groups was in the same range. Starting from day 8 p.i. rats in all groups showed a progressive weight loss by about 20-30% until day 14 p.i. Application of amantadine was found to be effective and significantly reduced neurological symptoms of EAE. We did not observed any neuroprotective effects of MPEP. The level of mGluR5 protein did not increase in early phase of EAE (4 day p.i.). However, starting from day 8 p.i. to day 25 p.i. we observed its significant elevation. The difference between control and examined group reached 20% at 25 day p.i. We did not observe significant differences in mGluR5 level between three experimental groups: EAE rats (control), MPEP-treated and amantadine-treated rats. Our results confirm the involvement of glutamate into pathogenesis of EAE. Although we noted changes in the expression of mGluR 5 during the course of EAE, MPEP was ineffective in reducing the symptoms of the disease. Results suggest the main role of NMDA glutamate receptors in the pathogenesis of EAE. Research was supported by funds from grant nr: NN401620038 from Polish Ministry of Scientific and Higher Education

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.155

Twórcy

autor

Sulkowski G.

• Medical Research Centre, Laboratory of Pathoneurochemistry, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland

autor

Dabrowska-Bouta B.

• Medical Research Centre, Laboratory of Pathoneurochemistry, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland

autor

Lenkiewicz A.

• Medical Research Centre, Laboratory of Pathoneurochemistry, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland

autor

Struzynska L.

• Medical Research Centre, Laboratory of Pathoneurochemistry, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland