Effects Of Swimming Exercise On Spatial Cognition Of TGF - β1 Transgenic Mice And Its Possible Mechanism

It has been demonstrated that appropriate amount of movement ameliorateslearning and memory ability in rodent and human. However, movement ofdifferent intensity generates differential effect on learning and memory.Literatures reported that swimming exercise affects learning and memory functionto some extent. The results in this study revealed that in the rat model ofswimming training in different intensity, expression level of TGF-β1inhippocampal tissues was differential. Based on this, we primarily explored theoptimal weight-bearing impacting on improvement of learning and memoryability and role of TGF-β1on amelioration of learning and memory induced byswimming exercise.Three month-old male mice of C57BL/6J strain were adopted in thisstudy. They were randomly divided into two groups: low TGF-β1expressiontransgenic group and wild type group, with21rats in each group. In each group,control group was set up respectively, in which no weight-bearing swimmingtraining group,1%weight-bearing swimming training group was set up, with7rats in each control. Following adaptability training for one week for all mice,mice in controls were bred routinely for8weeks, without swimming training. Asfor swimming groups, mice were subjected to weight-bearing swimming trainingfor8weeks (30min/6d/1w). After experiments were finished, Morris Water Mazewas employed to detect the ability of constant-bearing navigation for3dconcomitant with spatial exploration for1d. The gene expression level of PI3Kand AKT, which were known as the downstream molecules of TGF-β1wasexamined by RT-PCR. Moreover, the expression level of TGF-β1, PI3K and AKTand their phosphorylated protein was measured by Western blot.Results:1. Revealed by Morris Water Maze, the latency in two experimental groupsshowed that the weight-bearing time in1%weight-bearing swimming training group was the substantially shorter relative to control group(P<0.01). Theweight-bearing time in no-weight bearing swimming group was markedly longerthan that of the control (P<0.05). Morris Water Maze test showed that the timesfor mice to pass through the platform in1%weight-bearing swimming traininggroup was the most, no weight-bearing group was the second, while the least inthe control group (P<0.05).2. Results of gene expression: the genes of PI3K and AKT were expressed inall experimental groups. As for the level of PI3K gene expression in wild typegroup, the level was the highest in1%weight-bearing swimming training group,and the level of PI3K gene expression in swimming group all markedly higherthan those of the control groups(P<0.05). In the transgenic group, he level of PI3Kgene expression in no weight-bearing was the highest, which was significantlyhigher than that of control(P<0.05), the next was1%weight-bearing swimminggroup. The expression tendency of AKT gene was in accordance with PI3K.Notably, the level of AKT gene expression in transgenic groups were all higherthan those of wild type groups.3. Results of Western blot: the expression amount of PI3K and AKT inTGF-β1wild type mice was the highest, the next was no weight-bearingswimming group, in the1%weight-bearing group, this level was the lowest. Theexpression tendency of PI3K and AKT in transgenic group was completelycontrary to those of wild type groups. And expression level of PI3K and AKT intransgenic group was markedly lower relative to wild type group (P<0.05), that oftransgenic and no weight-bearing group was substantially lower than that of wildtype one (P<0.05). Ratio of P-PI3K/PI3K and P-AKT/AKT was corresponding tothe tendency of gene expression.Conclusions:Tail weight-bearing for8w effectively ameliorates the ability of learning andmemory, it is indicative that weight-bearing swimming training improves theability of learning and memory with intensity threshold that may be above1%.2. Morris Water Maze in transgenic C57BL/6J mice indicated that TGF-β1plays a critical role in improvement of learning and memory ability induced by swimming movement, it is possible that the regulation of PI3K and AKT geneexpression was involved in this procession.3. Tail weight-bearing for8w effectively ameliorates the ability of learningand memory. It is supposed that TGF-β1may be a two-directional regulator. Thedown regulation of TGF-β1level when the exercise intensity was added may be aprotective mechanism of sports fatigue.