These authors contributed equally to the work.
Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis
Article first published online: 23 AUG 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 1, pages 100–112, October 2012
How to Cite
Yao, S.-Q., Li, Z.-Z., Huang, Q.-Y., Li, F., Wang, Z.-W., Augusto, E., He, J.-C., Wang, X.-T., Chen, J.-F. and Zheng, R.-Y. (2012), Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis. Journal of Neurochemistry, 123: 100–112. doi: 10.1111/j.1471-4159.2012.07807.x
- Issue published online: 10 SEP 2012
- Article first published online: 23 AUG 2012
- Accepted manuscript online: 28 MAY 2012 08:39AM EST
- Received October 09, 2011; revised manuscript received may 14, 2012; accepted May 16, 2012.
- adenosine A1 receptors;
- adenosine A2A receptors;
- CD4+ T cells;
- experimental autoimmune encephalomyelitis (EAE);
- microglial cells;
- multiple sclerosis.
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 A1 receptor has been recently demonstrated, the role of the adenosine A2A receptor (A2AR) in development of EAE pathology is largely unknown. Using mice with genetic inactivation of the A2A receptor, we provide direct evidence that loss of the A2AR exacerbates EAE pathology in mice. Compared with wild-type mice, A2AR 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. A2AR 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 A2ARs triggers an important neuroprotective mechanism. Thus, the A2A receptor is a potential target for therapeutic approaches to multiple sclerosis.