Glutamate receptors antagonists attenuate neurological deficits and modulate neuroinflammation in Lewis rat subjected to experimental autoimmune encephalomyelitis

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

Abstrakty

EN

Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many aspects of multiple sclerosis (MS). Chronic or relapsing inflammation of the central nervous system results in the destruction of myelin sheath and cytokines play an important role in the pathogenesis of both MS and EAE. Myelin, oligodendrocytes and neurons are lost due to an inflammatory attack by leukocytes infiltrating the central nervous system (CNS) and releasing cytotoxic cytokines, anti CNS antibodies and large amounts of the excitatory neurotransmitter glutamate. Pharmacological studies have suggested that glutamate receptors mediate white matter injury in a variety of CNS diseases, including multiple sclerosis (MS). Memantine and amantadine are ionotropic glutamate receptors (iGluRs) antagonists. Memantine, a clinically applied drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rats subjected to experimental autoimmune encephalomyelitis (EAE). The aim of the present study was to investigate the effects of memantine and amantadine on the expression of proinflammatory cytokines such interleukin 1beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and various chemokines in the brain of EAE rats. Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western Blot were used to analyze the cytokine profile. We noticed increased expression of array of cytokines in experimental group when compared to the control. Dramatic increase of IL-1β, IL-6, TNF-α, and chemokines concentration corresponding to the intensity of neurological symptoms and loss of weight was observed in EAE rats. Administration of iGluR antagonists at an advanced stage of unremitting EAE resulted in amelioration of the disease. Cytokine analysis revealed that memantine significantly decreased the expression of interleukins: IL-6 (65%), IL-1β (60%) and TNF-α (45%) whereas treatment with amantadine reduced only the expression of IL-6 (60%) and TNF-α (15%) when compared to EAE animals. These results show that antagonists of iGlu receptors modulate the course of the disease by reducing the expression of proinflammatory cytokines thereby confirming the involvement of glutamate receptors into pathological mechanisms operating during EAE. This study was supported by grant nr NN401620038 from Polish Ministry of Science and Higher Education

Słowa kluczowe

EN

glutamate; receptor antagonist; neurological deficit; neuroinflammation; Lewis rat; rat; experimental autoimmune encephalomyelitis; pathomechanism; multiple sclerosis; central nervous system; pathogenesis

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.194

Twórcy

autor

Sulkowski G.

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

autor

Dabrowska-Bouta B.

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

autor

Chalimoniuk M.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Lenkiewicz A.

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

autor

Struzynska L.

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