MPTP-induced central dopamine depletion exacerbates experimental autoimmune encephalomyelitis (EAE) in C57BL mice.
It is obvious that the central nervous system plays a role in the regulation of an immune response. However, the mechanisms of this regulation are poorly understood. The goal of the present study was to examine the role of one of the neurotransmitters - dopamine, in this process. We used experimental autoimmune encephalomyelitis (EAE), an autoimmune disease with its effector phase in the CNS, as a model to study the effect of central dopamine depletion on the development of an immune response. Dopamine depletion was achieved by treatment with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropiridine (MPTP; 40 mg/kg), whereas EAE was elicited by immunization with MOG 35-55 (150 microg) in complete Freund's adjuvant (CFA), supplemented with Mycobacterium tuberculosis. As determined by HPLC, striatal dopamine contents in mice treated with MPTP were significantly lower compared to vehicle-treated controls. Remarkably, striatal depletion of dopamine prior to EAE induction resulted in an earlier onset of the disease and an augmentation of its clinical signs. Moreover, the striatal dopamine-depleted mice demonstrated an increased concentration of IL-1beta and decreased concentration of TGFbeta in the spinal cord, compared to EAE mice. Since MPTP itself does not have any direct effect on immune cells, it strongly suggests that the observed changes in EAE induction and progression after MPTP administration depended on lower dopamine level. Further studies are required to find out the cellular mechanism of the dopamine action.
Department of Experimental and Clinical Pharmacology, The Medical University of Warsaw, Krakowskie Przedmiescie 26/28, 00-927 Warsaw, Poland. ewazbi@amwaw.edu.pl
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Bałkowiec-Iskra
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Kurkowska-Jastrzebska
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Joniec
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Ciesielska
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Muszynska
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Przybyłkowski
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Członkowska
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Członkowski
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry; D004298:Dopamine / Q000032:analysis / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D007371:Interferon-gamma / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D020267:MPTP Poisoning / Q000150:complications*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics
D053583:Interleukin-1beta; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D004298:Dopamine