Glutamate (Gt) neurotoxicity contributes to a wide spectrum of neurological conditions. Loss of glutamate transporters leads to intracellular Gt accumulation. Amantadin (AMn) is a non-competitive N-methyl-D-aspartate (NMDA) antagonist that can partially inhibit Gt transporters and influence protein phosphatase 2A subunit B (PP-2A-B) activity. Herein, we investigate the potential of AMn administered in the early life stages to reverse the Gt-induced changes in the cerebral cortex in the rat model. We report that AMn can reverse Gt-induced structural changes in the brain cortex and increase PP-2A activity. Additionally, PP-2A-B activity in the AMn + Gt-treated group was comparable to controls. Moreover, administration of AMn leads to a decrease of apoptotic index in the Gt-treated individuals. We suggest that severe histopathological changes observed in Gt group could be attributed to the decreased PP-2A expression causing an imbalance between phosphatase and protein kinase activities and leading to a strong positive TUNEL reaction. We provide a short summary of the current state of knowledge regarding the role of PP-2A-B in the Gt-induced neurotoxicity and AMn treatment and discuss the potential of amantadine as a potential therapeutic agent.
Keywords: Amantadine; Cerebral cortex; Glutamate; PP-2A.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.