Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 129, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2019.104490
Keywords
A(2A) adenosine receptor; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Therapeutic time window; Neurobehavioral deficit; Macrophage/microglia
Categories
Funding
- National Natural Science Foundation of China [81571287, 81871026, 81371321, 81630040, 31771178]
- Guangdong Natural Science Foundation [2017A030313808]
- Shenzhen Science and Technology Innovation Committee Basic Science Research Grants [JCYJ20140417105742709, JCYJ20160301112230218, JI20180267, 20180306164718049]
- SUSTech Peacock Program Start-up Fund [22/Y01226109]
- SUSTech Brain Research Centre Fund
- Guangdong Innovation Platform of Translational Research for Cerebrovascular Diseases
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Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) affecting more than 2.5 million individuals worldwide. In the present study, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice were treated with adenosine receptor A(2A) antagonist SCH58261 at different periods of EAE development. The administration of SCH58261 at 11-28 days post-immunization (d.p.i.) with MOG improved the neurological deficits. This time window corresponds to the therapeutic time window for MS treatment. SCH58261 significantly reduced the CNS neuroinflammation including reduced local infiltration of inflammatory cells, demyelination, and the numbers of macrophage/microglia in the spinal cord. Importantly, SCH58261 ameliorated the EAE-induced neurobehavioral deficits. By contrast, the SCH58261 treatment was ineffective when administered at the beginning of the onset of EAE (i.e., 1-10 d.p.i). The identification of the effective therapeutic window of A(2A) receptor antagonist provide insight into the role of A(2A) receptor signaling in EAE, and support SCH58261 as a candidate for the treatment of MS in human.
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