Overexpression of P2X7R and early activation of cerebral microglia during experimental autoimmune encephalomyelitis

• Autorzy: Grygorowicz T. , Sulejczak D. , Rafalowska J. , Lenkiewicz A. , Struzynska L.
• Języki publikacji: EN

Abstrakty

EN

Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease which is one of the most frequent reasons of disabilities of young adults and a serious problem for modern medicine due to the unknown etiology. Experimental autoimmune encephalomyelitis (EAE) is a commonly used rodent model of MS. EAE is evoked by immunization of female Lewis rats with homogenate of guinea pigs’ spinal cord combined with complete Freund’s adjuvant and inactivated Mycobacterium tuberculosis. It is well known that during the development of MS and EAE, the immune system sensitizes against self myelin and the permeability of blood-brain barrier (BBB) increases what enables an inflow of immune cells into the central nervous system. The immune system attacks and destroys myelin in the brain and the spinal cord what further leads to degeneration of neurons. The aim of the study was to investigate the time-window of microglial activation, the level of proinflammatory cytokines (IL-1, IL-6, TNFα) and the status of BBB in the early stages of EAE. We correlated the results with the microglial and endothelial expression of purinergic P2X7 receptor which is known to play a role in inflammation due to a release of proinflammatory mediators. The results of microscopic analysis revealed the increased permeability of BBB. At day 2 and 4 p.i. we also observed decreased expression of claudin5 protein which is an important marker of BBB tightness. However, starting from day 6 p.i. we noticed significant upregulation of this protein expression. The early activation of microglial cells at day 4 post immunization (dpi), in asymptomatic phase of the disease, together with an increased level of proinflammatory cytokines were observed. These changes correlated temporary with overexpression of P2X7R which was noticed on microglial cells and pericytes of blood vessels in brains of EAE rats. The results suggest the critical role of this receptor in early events during EAE development.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: S
• Opis fizyczny: p.77

Twórcy

autor

Grygorowicz T.

• Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre PAS, Warsaw, Poland

autor

Sulejczak D.

• Department of Experimantal Pharmacology, Mossakowski Medical Research Center PAS, Warsaw, Poland

autor

Rafalowska J.

• Department of Experimental and Clinical Neurophatology, Mossakowski Medical Research Center PAS, Warsaw, Poland

autor

Lenkiewicz A.

• Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre PAS, Warsaw, Poland

autor

Struzynska L.

• Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre PAS, Warsaw, Poland

Uwagi

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