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

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Abstract

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.

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Data Availability

The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The research is self-funded. No funds were received.

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Authors and Affiliations

  1. Anatomy and Embryology Department, College of Medicine, Tanta University, Tanta, 31511, Egypt

    Ahmed S. Ahmed & Ehab M. Hantash

  2. Imam Muhammad Bin Saud Islamic University, Riyadh, Saudi Arabia

    Soha S. Zakaria

  3. Medical Biochemistry and Molecular Biology Department, College of Medicine, Tanta University, Tanta, 31511, Egypt

    Soha S. Zakaria

Authors
  1. Ahmed S. Ahmed
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  2. Ehab M. Hantash
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  3. Soha S. Zakaria
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Contributions

Ahmed S. Ahmed: data collection, data analysis, discussion of results, and paper editing. Ehab M. Hantash: discussion of results. Soha S Zakaria: data collection, data analysis.

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Correspondence to Ahmed S. Ahmed.

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Ethical Approval

The study protocol was approved by Research and Ethics Committee, Quality Assurance Unit, Faculty of Medicine, Tanta University, Egypt.

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Author has declared that no competing interests exist.

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Ahmed, A.S., Hantash, E.M. & Zakaria, S.S. Potential of Amantadine to Ameliorate Glutamate-Induced Pyramidal Cells Toxicity in Juvenile Rat’ Brain Cortex. Neurotox Res 39, 1203–1210 (2021). https://doi.org/10.1007/s12640-021-00365-7

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  • DOI: https://doi.org/10.1007/s12640-021-00365-7

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