| Objective:We observed and analyzed the behavioral performance about neural system of PrP-/- mice, hoping to find some related behavior characteristics, and thus to get a clue to further explore the function of PrP in neural system.Method:The mice were divided into WT group and PrP-/- group with the same age, sex ratio and health status. In the aspect of behavior characteristics analysis, at first the two groups of mice were tested by depression behavior evaluation, followed by sucrose preference test, open field test, tail suspending test and forced swimming test, which were detected whether PrP-/- mice had depressive tendency. Next, Morris water maze was employed to test the WT group and PrP-/- group of mice, evaluating the learning and memory ability of two groups to know whether they were different. Then, we carried out exercise test on the two groups of mice, including rotary rod test, beam walking test and coat hanger test to evaluate whether there were differences between their athletic abilities. In the aspect of the inquiry on cellular level, we acquired the WT group and PrP-/- group newborn mice hippocampal cells. After acted by different concentration of NMDA for 5 minutes, the cells were added in Fluo 4-AM as calcium ion probe to determine free calcium ion concentrations by enzyme labeling instrument. We also used different concentrations of NMDA acting two groups of cells for 6 days, following by MTT method to determine cells viability. We determined the expression levels of SK channel in PrP-/- and WT hippocampal neurons by Western blotting, to analyze whether the deletion of PrP can affect the expression of SK channel in the hippocampus.Result:In the evaluation of depression behavior, the depression indexes of PrP-/- mice on sucrose preference test, open field test and tail suspending test were significantly higher than those of WT mice. But in forced swimming test, the depression index of PrP-/- mice was significantly lower than that of WT mice. In Morris water maze test, prp-/- group’s performances in spatial search test and navigation test were significantly lower than those in WT mice. At the same time, the performances of PrP-/- mice in the rotary rod test, beam walking test and coat hanger test were also significantly lower than WT group. On the detection of cell level, it was found that there was no significant difference about the concentration of free calcium ions between the two groups of cells after three concentrations of NMD A acting for 5 min. However, after six days acted by high concentrations of NMDA the survival situation of PrP-/- cells were significantly lower than that of WT cells. The results of Western blotting showed that there was no significant difference in the expression of SK channel between PrP-/- and WT cells.Conclusion:Behavioral evaluation results suggest that PrP-/- mice may have a tendency of depression, but PrP-/- mouse is not a kind of natural depression model. The learning and memory ability and motor ability of PrP-/- mice may have some defects. The results on the cellular level show that hippocampal cells lacking of PrP may be more susceptible to the damage caused by NMDA. It suggestes that NMDA receptor on the hippocampal neurons lacking of PrP may have increased sensitivity, which is consistent with the behavioral assessment of learning and memory ability of PrP-/- mice.The concentration of free calcium ion in the PrP-/- hippocampal neurons had no significant difference compared with WT, which may indicates that the phenomenon that PrP-/- hippocampal neurons are more prone to injury caused by high concentrations of NMDA may results from the other specific pathways and mechanisms which need to be further explored. In addition, there was no significant difference in the expression level of SK channel between PrP-/- and WT hippocampal neurons, indicating that the deletion of PrP may not affect the expression level of SK channel in hippocampal neurons. |
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