MicroRNA-328a Regulates The Cognitive Function Of Pentylenetetrazole-induced Epileptic Rats

【Objective】Memory impairment in people with epilepsy have aroused a lot of attention from researchers.From the previous study,mi R-328 a was downregulated in the hippocampus of epileptic rats with cognitive dysfunction.Whether the down-regulation of miR-328 a contributes to the memory impairment and the underlying mechanism remain unknown.To confirm the variation of miR-328 a and study the underlying mechanism,we evaluated the learning and memory ability of all rats and the molecular variation in the hippocampus through following methods.【Methods】48 SD male rats were separated into 4 groups as follows: a sham group,a PTZ kindled group,a mi R-328 a antagomir group and an antagomir-control group(n = 12 for each).After 28 days,their learning and memory abilities were evaluated using Morris Water Maze test.RT-qPCR,Targetscan were performed to assay the expression of miR-328 a and predicttarget genes.Western Blotting was conducted to investigate the expression of corresponding proteins.【Results】(1)Morris Water Maze test:(1)The escape latency was reduced gradually during 5 training days.(2)Compared to the sham group,latency of the PTZ group on the 5th day was longer(P<0.05).No statistical differences were shown between the antagomir-control group and the PTZ group(P>0.05).Compared to the antagomir-control group,the 5th-day latency of the antagomir group was longer(P<0.05).(3)On the 6th day,the target quadrant time of the PTZ group was shorter than that of the sham group(P<0.05).No statistical differences were shown between the antagomir-control group and the PTZ group(P>0.05).Compared to the antagomir-control group,the target quadrant time of the antagomir group was shorter(P<0.05).(4)The target quadrant distance of the PTZ group was shorter than that of the sham group(P<0.05).No statistical differences were shown between the antagomir-control group and the PTZ group(P>0.05).Compared to the antagomir-control group,the target quadrant distance of the antagomir group was shorter(P<0.05).(2)RT-qPCR: Compared to the PTZ group,the hippocampal miR-328 a levels of the sham group were higher(P<0.05).No statistical differences were shown between the antagomir-control group and the PTZ group(P>0.05).Compared to the antagomir group,the hippocampal miR-328 a levels of the antagomir-control group were higher(P<0.05).(3)Targetscan: Conserved binding sites to miR-328 a were shown on 408-415 nt in the 3’ untranslated region of BACE.(4)Western blotting: The hippocampal BACE levels of the PTZ group were higher than those of the sham group(P<0.05).No statistical differences were shown between the antagomir-control group and the PTZ group(P>0.05).Compared to the antagomir-control group,the hippocampal BACE levels of the antagomir group was higher(P<0.05).The hippocampal BACE levels increased0.65-fold in the PTZ group compared to the sham group,and it increased 0.38-fold in the antagomir group compared to the antagomir-control group.【Conclusions】(1)The down-regulation of miR-328 a in the hippocampus was confirmed.(2)MiR-328 a regulated the cognitive function of epileptic rats through upregulating the hippocampal BACE expression.(3)There might be a potential link between Alzheimer’s disease and epilepsy.