The role of P2X7R in activation of glial cells during the early phase of experimental autoimmune encephalomyelitis

• Autorzy: Grygorowicz T. , Welniak-Kaminska M. , Lenkiewicz A. , Struzynska L.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Multiple sclerosis (MS) is an autoimmune, neuroinflammatory disease resulting in progressive demyelinization. Glial cells are important players during development of inflammationwithin central nervoussystem.Underinflammatory signals astroglia and microglia change their morphology and up-regulate expression of GFAP and Iba1 proteins, respectively. Both of these cell populations express purinergic receptor P2X7. The aim of the study was to investigate the effect of P2X7R antagonist (Brilliant Blue G, BBG) on the course of experimental autoimmune encephalomyelitis (EAE) with the focus on the influence of BBG-treatment on the reactive gliosis. METHODS: EAE, an animal model of MS, was evoked by the immunization of Lewis rats with guinea pigs’ spinal cord homogenate with complete Freund’s adjuvant. BBG (50 mg/kg) was administered daily from day 0 to day 6 post immunization through the jugular catheter. RESULTS: Immunofluorescent analysis of brain slices showed the activation of astroglial and microglial cells in EAE rats, but not in EAE rats treated with BBG. The expression of GFAP was 5,5 times higher in EAE than in EAE+BBG group at the asymptomatic phase and 3.1 times higher at symptomatic phase of the disease. These results were confirmed by western blot analysis. Expression of Iba1 was 5.4 times and 3.6 times higher in the EAE than in EAE+BBG group at the asymptomatic and symptomatic phases, respectively. The effects of BBG treatment on the expression of proinflammatory cytokines such as IL-1β, IL-6, TNF-α were determined by western blot method. The level of these cytokines was significantly lower in EAE+BBG group than in EAE animals and remained similar to that observed in control rats. CONCLUSIONS: Blockade of P2X7R during the course of EAE results in: (1) improved condition of Animals; (2) decreased activation of astro- and microglia; (3) decreased level of proinflamatory cytokines Supported by Polish National Science Centre, grant nr: DEC-2012- /05/N/NZ4/02191.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S68-S69

Twórcy

autor

Grygorowicz T.

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

autor

Welniak-Kaminska M.

• Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Lenkiewicz A.

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

autor

Struzynska L.

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