Qi Huang1, Xixia Liu1, Yuan Wu2, Yuhan Liao1, Yiqing Huang1, Xing Wei1, Meigang Ma1. 1. Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 6th Shuangyong Road, Nanning, Guangxi, China. 2. Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 6th Shuangyong Road, Nanning, Guangxi, China. Electronic address: Nwuyuan90@163.com.
Abstract
OBJECTIVE: Our group has previously reported the role of P38 mitogen-activated protein kinase (MAPK) pathway in the memory impairment of pentylenetetrazole (PTZ)-kindled rats. However, any contribution of p38 MAPK pathways to the cognitive dysfunction of PTZ-kindled rats remains unclear. The objective of this study is to verify the relationship between p38 MAPK pathway and cognitive function of epileptic rats, and discuss probable mechanisms. METHODS: Thirty male SD rats were divided into three groups, namely, PTZ, inhibitor, and sham groups. All rats except those from the sham group were treated with PTZ to establish temporal lobe epilepsy (TLE) models, whereas the P38 MAPK inhibitor SB 203580 was given to the inhibitor group. Morris water maze test was performed to assay their learning and memory abilities. The levels of phosphorylated p38 (p-p38) and caspase 3 were confirmed using Western blot. RESULTS: In the probe test of water maze, the PTZ group had the longest escape latency and least time to pass through the platform. Compared with the PTZ group, the inhibitor group had better performance in escape latency and spatial probe tests. Performance in the water maze test corresponded with the level of p-p38 and caspase 3 in hippocampus. We also found that the down-regulation of p-p38 in the inhibitor group led to down-regulated levels of caspase 3. CONCLUSIONS: P38 MAPK pathway contributed to cognitive damage in PTZ-induced epilepsy via apoptosis cascade.
OBJECTIVE: Our group has previously reported the role of P38 mitogen-activated protein kinase (MAPK) pathway in the memory impairment of pentylenetetrazole (PTZ)-kindled rats. However, any contribution of p38 MAPK pathways to the cognitive dysfunction of PTZ-kindled rats remains unclear. The objective of this study is to verify the relationship between p38 MAPK pathway and cognitive function of epilepticrats, and discuss probable mechanisms. METHODS: Thirty male SD rats were divided into three groups, namely, PTZ, inhibitor, and sham groups. All rats except those from the sham group were treated with PTZ to establish temporal lobe epilepsy (TLE) models, whereas the P38 MAPK inhibitor SB 203580 was given to the inhibitor group. Morris water maze test was performed to assay their learning and memory abilities. The levels of phosphorylated p38 (p-p38) and caspase 3 were confirmed using Western blot. RESULTS: In the probe test of water maze, the PTZ group had the longest escape latency and least time to pass through the platform. Compared with the PTZ group, the inhibitor group had better performance in escape latency and spatial probe tests. Performance in the water maze test corresponded with the level of p-p38 and caspase 3 in hippocampus. We also found that the down-regulation of p-p38 in the inhibitor group led to down-regulated levels of caspase 3. CONCLUSIONS:P38 MAPK pathway contributed to cognitive damage in PTZ-induced epilepsy via apoptosis cascade.