Genetic inactivation of the adenosine A2Areceptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis
Journal of Neurochemistry. 2012-08-23; 123(1): 100-112
DOI: 10.1111/j.1471-4159.2012.07807.x
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Yao SQ(1), Li ZZ, Huang QY, Li F, Wang ZW, Augusto E, He JC, Wang XT, Chen JF,
Zheng RY.
Author information:
(1)Department of Neurology, the First Affiliated Hospital and Research Institute
of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang, PR
China.
Studies with multiple sclerosis patients and animal models of experimental
autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors
in modulation of neuroinflammation and brain injury. Although the involvement of
the A(1) receptor has been recently demonstrated, the role of the adenosine
A(2A) receptor (A(2A)R) in development of EAE pathology is largely unknown.
Using mice with genetic inactivation of the A(2A) receptor, we provide direct
evidence that loss of the A(2A)R exacerbates EAE pathology in mice. Compared
with wild-type mice, A(2A)R knockout mice injected with myelin oligodendroglia
glycoprotein peptide had a higher incidence of EAE and exhibited higher
neurological deficit scores and greater decrease in body weight. A(2A)R knockout
mice displayed increased inflammatory cell infiltration and enhanced microglial
cell activation in cortex, brainstem, and spinal cord. In addition,
demyelination and axonal damage in brainstem were exacerbated, levels of Th1
cytokines increased, and Th2 cytokines decreased. Collectively, these findings
suggest that extracellular adenosine acting at A(2A)Rs triggers an important
neuroprotective mechanism. Thus, the A(2A) receptor is a potential target for
therapeutic approaches to multiple sclerosis.
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for
Neurochemistry.