Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Prevalence of glutamate receptor subunit 2 (GluR2)-lacking Ü-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is a hallmark of excitotoxicity-related neurodegenerative diseases. Topiramate (TOP) is a structurally novel anticonvulsant with a well-known modulatory effect on AMPA/kainate subtypes of glutamate receptors. Levetiracetam (LEV) is a unique anti-epileptic acting mainly via inhibition of glutamate release. The present study aimed at investigating the neuroprotective potentials of TOP and LEV on 3-nitropropionic acid (3-NP)-induced striatal neurodegeneration and Huntington's disease (HD)-like symptoms. Rats were injected with 3-NP (10 mg/kg/i.p.) for 14 days, TOP (50 mg/kg/p.o.) and LEV (100mg/ kg/p.o.) were given once a day, 1 h before 3-NP. Administration of TOP and LEV amended 3-NP induced changes in neurobehavioral performance, striatal neurotransmitters levels and histopathological injury. 3-NP control rats showed a significant ablation in the mRNA expression of Ca2+-impermeable Glu2R subunit along with an elevation in its regulatory protein PICK1, an effect that was largely reversed by TOP and LEV

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