Chronic caffeine treatment protects against experimental autoimmune encephalomyelitis in mice: therapeutic window and receptor subtype mechanism.

Autor: Wang T; Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical University, PR China., Xi NN; Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical University, PR China., Chen Y; Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical University, PR China., Shang XF; Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical University, PR China., Hu Q; Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical University, PR China., Chen JF; Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical University, PR China; Department of Neurology, Boston University School of Medicine, USA. Electronic address: chenjf@bu.edu., Zheng RY; Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical University, PR China. Electronic address: zhengry1949@163.com.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2014 Nov; Vol. 86, pp. 203-11. Date of Electronic Publication: 2014 Jul 11.
DOI: 10.1016/j.neuropharm.2014.06.029
Abstrakt: Chronic treatment with caffeine, the most widely consumed psychoactive drug and a non-selective antagonist of adenosine receptors, can protection against myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In this study, we investigated the mechanism underlying caffeine-mediated neuroprotection against EAE by determining the effective therapeutic time-window of caffeine and the involvement of adenosine A2A and A1 receptor. We found that administration of caffeine during the effector phase (10 → 20 days post-immunization, d.p.i., corresponding to appearance of neurological deficits) but not the induction phase (0 → 10 d.p.i., before the appearance of ascending flaccid paralysis) significantly ameliorated EAE-induced neurobehavioral deficits, reduced the infiltration of inflammatory cells into the spinal cord and reduced the demyelination of spinal cord. Furthermore, genetic deletion of the A2AR exacerbated MOG-induced brain damage and caffeine administering to A2AR knockout mice reversed this EAE pathology by acting at non-A2AR target. The protective effect of chronic caffeine treatment was associated with up-regulation of brain A1R (but not A2AR). The identification of the effective therapeutic window of caffeine at the effector phase and clarification of non-A2AR target (likely A1R) in caffeine action in EAE models advance the therapeutic prospective that chronic caffeine consumption may attenuate brain damage in MS.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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