Amantadine’s Potential To Mitigate GlutamateInduced Toxicity In Pyramidal Cells Of The Juvenile Rat Brain Cortex

Glutamate (Gt) neurotoxicity is implicated in a wide range of neurological conditions, with the loss of glutamate transporters leading to intracellular Gt accumulation. Amantadine (AMn), a non-competitive N-Methyl-D-aspartate (NMDA) antagonist, can partially inhibit Gt transporters and modulate Protein Phosphatase 2A subunit B (PP-2A-B) activity. This study explores the potential of early-life AMn administration to counteract Gt-induced changes in the cerebral cortex using a rat model. Our findings indicate that AMn can reverse Gt-induced structural alterations in the brain cortex and enhance PP-2A activity. Additionally, PP-2A-B activity in the AMn+Gt-treated group was comparable to control levels. Furthermore, AMn administration reduced the apoptotic index in Gt-treated individuals. We propose that the severe histopathological changes observed in the Gt group may be attributed to decreased PP-2A expression, disrupting the balance between phosphatase and protein kinase activities and resulting in a strong positive TUNEL reaction. This study provides a concise overview of the current understanding of PP-2A-B’s role in Gt-induced neurotoxicity and AMn treatment while highlighting amantadine’s potential as a therapeutic agent. Keywords : Amantadine; Glutamate; cerebral cortex; PP-2A.