Potential of Amantadine to Ameliorate Glutamate-Induced Pyramidal Cells Toxicity in Juvenile Rat' Brain Cortex

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.

Automated summary

The study found that amantadine can reverse the structural changes induced by glutamate in the rat brain cortex and increase the activity of protein phosphatase 2A subunit B. Additionally, the administration of amantadine led to a decrease in the apoptotic index in the treated individuals. This indicates the potential of amantadine as a therapeutic agent.