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MicroRNA-328a regulates water maze performance in PTZ-kindled rats.

Abstract
The down-regulation of microRNA-328a (miR-328a) in pentylenetetrazole (PTZ)-kindled rats with memory impairment was demonstrated in our previous study, while any contribution of miR-328a to cognitive dysfunction of PTZ-kindled rats remains unknown. In this study we have investigated the effect and the underlying mechanism of miR-328a on the cognitive function in PTZ-kindled rats. 48 SD male rats were divided into 4 groups as follows: a PTZ kindled group, a miR-328a antagomir group, an antagomir-control group, and a sham group (n=12 for each). All rats except those from the sham group were treated with PTZ 14 times at intervals of 48h to establish the temporal lobe epilepsy (TLE) models, and miR-328a antagomir was given to the antagomir group as a treatment by lateral-ventricle injection the day after the first injection of PTZ. Morris water maze (MWM) test was performed to assay their learning and memory abilities. The down-regulation of miR-328a in the PTZ group was confirmed using RT-qPCR and the expression of miR-328a was diminished after antagomir treatment (P<0.05). In the probe test of water maze, the time and distance of the PTZ group were both shorter than those of the sham group (P<0.05), and those of the antagomir-control group were both longer than those of the antagomir group (P<0.05). In addition, we found that with the down-regulation of miR-328a, the levels of Beta-site APP-cleaving enzyme (BACE), which is a bioinformatics-predicted target of miR-328a, were up-regulated. These findings suggest that miR-328a may play a role in memory dysfunction in PTZ-kindled rats by regulating the BACE levels and this links the PTZ model with Alzheimer's disease.
AuthorsYuhan Liao, Yiqing Huang, Xixia Liu, Chun Luo, Donghua Zou, Xing Wei, Qi Huang, Yuan Wu
JournalBrain research bulletin (Brain Res Bull) Vol. 125 Pg. 205-10 (07 2016) ISSN: 1873-2747 [Electronic] United States
PMID27444122 (Publication Type: Journal Article)
CopyrightCopyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antagomirs
  • Bcl9l protein, rat
  • GTPase-Activating Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • Syngap1 protein, rat
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, rat
  • GTP-Binding Proteins
  • Pentylenetetrazole
Topics
  • Amyloid Precursor Protein Secretases (metabolism)
  • Animals
  • Antagomirs (pharmacology)
  • Aspartic Acid Endopeptidases (metabolism)
  • Disease Models, Animal
  • Down-Regulation (drug effects)
  • Epilepsy, Temporal Lobe (chemically induced)
  • GTP-Binding Proteins (metabolism)
  • GTPase-Activating Proteins (metabolism)
  • Kindling, Neurologic (drug effects, physiology)
  • Male
  • Maze Learning (drug effects, physiology)
  • MicroRNAs (chemistry, genetics, metabolism)
  • Neoplasm Proteins (metabolism)
  • Pentylenetetrazole (toxicity)
  • Rats
  • Rats, Sprague-Dawley

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