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

Abstract

In recent years, inactivation of A2A adenosine receptors has been emerged as a novel strategy for treatment of several neurodegenerative diseases. Although numerous studies have shown the beneficial effects of A2A receptors blockade on spatial memory, the impacts of selective adenosine A2A receptors on memory performance has not yet been examined in the context of demyelination. In the present study, we evaluated the effect of A2A 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 A2A 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 A2A receptor antagonist. Collectively, the results of this study suggest that A2A receptor blockade can improve the spatial memory and protect myelin sheath, which might be considered as a novel therapeutic approach for multiple sclerosis disease.

• Authors: Atefeh Akbari, Mohsen Khalili-Fomeshi, Manouchehr Ashrafpour, Ali Akbar Moghadamnia, Maryam Ghasemi-Kasman
• Journal: Life sciences (Life Sci) Vol. 205 Pg. 63-72 (Jul 15 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 29730168 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
• Adenosine A2 Receptor Antagonists
• Lysophosphatidylcholines
• Pyrimidines
• Receptor, Adenosine A2A
• Triazoles

Topics

• Adenosine A2 Receptor Antagonists (adverse effects, therapeutic use)
• Animals
• Astrocytes (drug effects)
• Demyelinating Diseases (chemically induced, drug therapy, pathology)
• Hippocampus (pathology)
• Injections, Intraventricular
• Lysophosphatidylcholines
• Macrophage Activation (drug effects)
• Male
• Maze Learning (drug effects)
• Memory Disorders (etiology, psychology)
• Microglia (drug effects)
• Pyrimidines (adverse effects, therapeutic use)
• Rats
• Rats, Wistar
• Receptor, Adenosine A2A
• Spatial Memory (drug effects)
• Triazoles (adverse effects, therapeutic use)