Neuroprotective and anti-inflammatory effects of the adenosine A2A receptor antagonist ST1535 in a MPTP mouse model of Parkinson's disease
Article first published online: 27 JUL 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 65, Issue 3, pages 181–188, March 2011
How to Cite
Frau, L., Borsini, F., Wardas, J., Khairnar, A. S., Schintu, N. and Morelli, M. (2011), Neuroprotective and anti-inflammatory effects of the adenosine A2A receptor antagonist ST1535 in a MPTP mouse model of Parkinson's disease. Synapse, 65: 181–188. doi: 10.1002/syn.20833
- Issue published online: 28 DEC 2010
- Article first published online: 27 JUL 2010
- Accepted manuscript online: 27 JUL 2010 12:00AM EST
- Manuscript Accepted: 22 JUN 2010
- Manuscript Received: 19 FEB 2010
- Ministry of Science and Higher Education, Warszawa, Poland. Grant Number: N N401 1137 33
- neuron degeneration;
- substantia nigra compacta
Adenosine A2A receptor antagonists are one of the most attractive classes of drug for the treatment of Parkinson's disease (PD) as they are effective in counteracting motor dysfunctions and display neuroprotective and anti-inflammatory effects in animal models of PD. In this study, we evaluated the neuroprotective and anti-inflammatory properties of the adenosine A2A receptor antagonist ST1535 in a subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. C57BL/6J mice were repeatedly administered with vehicle, MPTP (20 mg/kg), or MPTP + ST1535 (2 mg/kg). Mice were sacrificed three days after the last administration of MPTP. Immunohistochemistry for tyrosine hydroxylase (TH) and cresyl violet staining were employed to evaluate dopaminergic neuron degeneration in the substantia nigra pars compacta (SNc) and caudate-putamen (CPu). CD11b and glial fibrillary acidic protein (GFAP) immunoreactivity were, respectively, evaluated as markers of microglial and astroglial response in the SNc and CPu. Stereological analysis for TH revealed a 32% loss of dopaminergic neurons in the SNc after repeated MPTP administration, which was completely prevented by ST1535 coadministration. Similarly, CPu decrease in TH (25%) was prevented by ST1535. MPTP treatment induced an intense gliosis in both the SNc and CPu. ST1535 totally prevented CD11b immunoreactivity in both analyzed areas, but only partially blocked GFAP increase in the SNc and CPu. A2A receptor antagonism is a new opportunity for improving symptomatic PD treatment. With its neuroprotective effect on dopaminergic neuron toxicity induced by MPTP and its antagonism on glial activation, ST1535 represents a new prospect for a disease-modifying drug. Synapse, 2010. © 2010 Wiley-Liss, Inc.