The effect on seizure susceptibility, learning, memory and injury of mice hippocampal neurons by disturbing zinc metabolism
LI Xia, LIU Ming-chen, JIA Yu-shan, LV Ming-pu, ZHANG Li
Chinese Journal of Clinical Anatomy ›› 2019, Vol. 37 ›› Issue (1) : 45-50.
The effect on seizure susceptibility, learning, memory and injury of mice hippocampal neurons by disturbing zinc metabolism
Objective To study the effects of disturbed zinc metabolism on the epilepsy susceptibility, learning, memory ability and hippocampal neuron injury of the epilepsy mice by clioquinol pre-treatment. Methods Seventy-two CD-1 mice were randomly divided into a control group, an epilepsy group and a clioquinol group. Mice in clioquinol group were injected intraperitoneally with clioquinol 10 mg·kg-1·d-1. Mice in the control and epilepsy group were given saline instead. One week later, mice in the epilepsy and clioquinol group were treated intraperitoneally with pilocarpine 300 mg/kg to establish the epilepsy model. Mice in he control group were given saline instead. Afterwards, the period of incidence, incubation and seizure level were observed in 90 min after pilocarpine injection. Tissues were obtained on the 7th day. Autometallography was used to detect the distribution of zinc in hippocampus. Nissl staining was used to check the morphological changes of hippocampal neurons. ELISA detection was used to check the level of S-100β and neuronspecific enolase (NSE) protein in serum and cerebrospinal fluid. One month later, Mirror maze experiment was used to detect the escape latency and time in correct quadrant. Results Compared with the epilepsy group, the incidence and seizure level was increased and incubation period shortened in clioquinol group (P<0.01). The zinc level was lower in the clioquinol group than the epilepsy group (P<0.01). There were much more hippocampal neurons in the clioquinol group. The injury of neurons was remedied in the clioquinol group. The expression of S-100β and NSE protein in serum and cerebrospinal fluid decreased significantly in the clioquinol group (P<0.01). Mirror experiment showed that the escape latency was shorter and time in correct quadrant were longer than in epilepsy group (P<0.01). Conclusion Clioquinol can lower the zinc accumulation in the epilepsy mice hippocampus, increase the epilepsy susceptibility, inhibit the injury of neurons and improve the learning and memory capability.
Clioquinol; / Epilepsy; / Hippocampus; / Zinc; / Injury
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