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

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.