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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Disease Models, Animal, Dizocilpine Maleate, Epilepsy, Temporal Lobe, Excitatory Amino Acid Antagonists, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, Hippocampus, Humans, Male, MicroRNAs, Muscarinic Agonists, Oligonucleotide Array Sequence Analysis, Pilocarpine, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate, Statistics, Nonparametric.
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Does microRNA-139-5p negatively regulate NR2A-containing NMDA receptor in the rat pilocarpine model and patients with temporal lobe epilepsy? Context: Regulation of N-methyl-d-aspartate (NMDA) subunits NR2A and NR2B expression during status epilepticus (SE) remains incompletely understood. Here we explored the role of brain-enriched microRNA (miR)-139-5p in this process. miRNA microarray was performed to examine changes in miRNA expression in the rat pilocarpine model following NMDA-receptor blockade. The dynamic expression patterns of miR-139-5p, NR2A, and NR2B levels were measured in rats during the three phases of temporal lobe epilepsy (TLE) development using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Similar expression methods were applied to hippocampi obtained from patients with TLE and from normal controls. Moreover, miR-139-5p agomir and antagomir were utilized to explore the role of miR-139-5p in determining NMDA-receptor subunit expression patterns. We identified 18 miRNAs that were significantly altered in the rat pilocarpine model following NMDA-receptor blockade. Of these, miR-139-5p was significantly up-regulated and Grin2A was predicted as its potential putative target. In patients with TLE, miR-139-5p expression was significantly down-regulated, whereas NR2A and NR2B levels were significantly up-regulated. In the rat model of SE, miR-139-5p expression was down-regulated while NR2A was up-regulated in the acute and chronic phases, but not in the latent phase. NR2B expression was up-regulated during the three phases of TLE development. Overexpression of miR-139-5p decreased, whereas depletion of miR-139-5p enhanced the expression levels of NR2A, but not NR2B, induced by pilocarpine treatment. Of interest, NMDA nonselective antagonist and NR2A selective antagonist enhanced miR-139-5p levels suppressed by pilocarpine treatment, whereas the NR2B selective antagonist was ineffective.
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These findings elucidate the potential role of miR-139-5p in NMDA-receptor involvement in TLE development and may provide novel therapeutic targets for the future treatment of TLE. Final Decision: yes