Adenosine A2A receptor blockade attenuates spatial memory deficit and extent of demyelination areas in lyolecithin-induced demyelination model

Abstract

In recent years, inactivation of A_2A adenosine receptors has been emerged as a novel strategy for treatment of several neurodegenerative diseases. Although numerous studies have shown the beneficial effects of A_2A receptors blockade on spatial memory, the impacts of selective adenosine A_2A receptors on memory performance has not yet been examined in the context of demyelination. In the present study, we evaluated the effect of A_2A receptor antagonist SCH58261 on spatial memory and myelination in an experimental model of focal demyelination in rat fimbria. Demyelination was induced by local injection of lysolecithin (LPC) 1% (2 μl) into the hippocampus fimbria. SCH58261 (20 μg/0.5 μl or 40 μg/0.5 μl) was daily injected intracerebroventricularly (i.c.v.) for 10 days post LPC injection. The Morris water maze test was used to assess the spatial learning and memory on day 6 post lesion. Myelin staining and immunostaining against astrocytes/microglia were carried out 10 days post LPC injection. The administration of adenosine A_2A receptor antagonist prevented the spatial memory impairment in LPC receiving animals. Myelin staining revealed that application of SCH58261 reduces the extent of demyelination areas in the fimbria. Furthermore, the level of astrocytes and microglia activation was attenuated following administration of A_2A receptor antagonist. Collectively, the results of this study suggest that A_2A receptor blockade can improve the spatial memory and protect myelin sheath, which might be considered as a novel therapeutic approach for multiple sclerosis disease.

Keywords: A(2A) receptor antagonist; Adenosine; Demyelination; Fimbria; Lysolecithin; Spatial memory.