2R,4R-APDC, a Metabotropic Glutamate Receptor Agonist, Reduced Neuronal Apoptosis by Upregulating MicroRNA-128 in a Rat Model After Seizures

Neurochemical Research
Ya-Bo FengHong Yao

Abstract

This study aimed to study the protective effect of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), a selective metabotropic glutamate receptor agonist, against hippocampal neuronal apoptosis induced by seizures in a rat model of pilocarpine-induced epilepsy. The Morris water maze test was used to assess the spatial memory abilities of epileptic rats with or without 2R,4R-APDC treatment. TUNEL assay was performed to examine neuronal apoptosis in hippocampus. Western blot was conducted to evaluate changes in the levels of caspase-3 and caspase-9 in hippocampus. Real-time PCR was used to determine the levels of microRNA-128 (miR-128) in hippocampus. The results of the Morris water maze test showed that the 2R,4R-APDC treatment reduced the escape latencies and swimming lengths of rats after seizures. The TUNEL assay showed that 2R,4R-APDC significantly counteracted seizure-induced cell apoptosis. The western blot confirmed this finding, demonstrating that the levels of cleaved caspase-3 and cleaved caspase-9 were potently decreased by 2R,4R-APDC in rat hippocampus after seizures. In addition, 2R,4R-APDC upregulated miR-128 expression levels in the hippocampus. A miR-128 mimic or inhibitor decreased or increased the perce...Continue Reading

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Citations

Jun 30, 2019·Biochemical Pharmacology·Davide MarangonDavide Lecca

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis