Mir-181A Influences The Cognitive Function Of Epileptic Rats Induced By PTZ

(Objective] More and more studies have confirmed that the abnormal expression and function of microRNAs have close relationship with the learning and memory impairment of nervous system. Our previous study showed that the expression of miR-181a in memory impairment group of pentylenetetrazol (PTZ)-induced epileptic rats was up-regulated, but whether miR-181a influenced the cognitive function of PTZ-induced epileptic rats remains unknown. Therefore, we investigated the role of miR-181a in the cognitive function of PTZ-induced epileptic rats.I Methods] A model of temporal lobe epilepsy (TLE) was induced via PTZ kindling in SD male rats. The epileptic rats were divided into Epilepsy group, Agomir-control group, miR-181a agomir group,12 rats for each.12 rats were used as sham group. After 28 days, the rats were subjected to Morris Water Maze test, RT-qPCR, TUNEL and western blot.[Results](1) Morris Water Maze test:In the place navigation test, with the increasing of training days, the escape latency of every group was shortened gradually. The escape latency of other groups were higher than the sham group in the 5th day (P<0.05). The escape latency of miR-181a agomir group was higher than that of Epilepsy group (P＜0.05). Compared miR-181a agomir group with Agomir-control group, they didn’t have obvious differences (P>0.05).In the 6th day, we removed the platform and conduct Spatial probe test. The data showed that compared with the sham group, crossing times of other groups were less than that of the sham group. The percentage of time that rats stayed in target quadrant in epilepsy group and miR-181a agomir group were less than that of the sham group (P<0.05). Compared with Agomir-control group, the percentage of time that rats stayed in target quadrant in miR-181a agomir group was significantly decreased (P＜0.05).(2) RT-qPCR:Compared with the sham group, the expression of miR-181a in other groups were up regulated obviously (P＜0.05). The results indicated that the levels of miR-181a were increased after epilepsy. Compared to the Epilepsy group and the Agomir-control group, the expression of miR-181a in miR-181a agomir group was increasd significantly (P＜0.05).(3) TUNEL:Compared with the sham group, the apoptotic cells of other groups were obviously increased (P＜0.05), which may supported that the apoptosis in hippocampus was increased after epilepsy. Compared with the Epilepsy group, the apoptotic cells of miR-181a agomir group increased 12.83% (P＜0.05). Comparing the miR-181a agomir group with the Agomir-control group, the apoptotic cells increased 7.67% (P>0.05). The data indicated that over-expression of miR-181a may increase the apoptosis of the hippocampus.(4) western blot:Compared with the sham group, the expressions of Bcl-2 protein in other groups were decreased (P＜0.05). Compared with the Agomir-control group, the expression of Bcl-2 protein in miR-181a agomir group was decreased obviously (P<0.05). These findings showed that over-expression of miR-181a significantly reduced Bcl-2 protein level.[Conclusions] Our findings suggest that miR-181a may play a role in impairing the cognitive function of PTZ-induced epileptic rats, and miR-181a could decrease the Bcl-2 protein and induce the apoptosis in the hippocampus that might be the way to impair cognitive function.