Effects Of "Physical-mental Exercise" On Hippocampal Neurons And Mitochondrial Dynamics-related Protein In Aging Mice

Object:To investigate the effect of the intervention of "physical-mental exercise" on the spatial memory,hippocampal neurons and mitochondria in aging mice,and to explore the mitochondrial dynamics mechanism of "physical-mental exercise" for improving aging.Methods:48 18-month-old SPF female mice are divided into old control group(OC),old physical exercise group(PE),old mental exercise group(ME)and old physical-mental exercise group(PME)by random number table method.12 3-month-old mice are taken for young control group(YC).12 mice in each group.YC and OC are fed in standard environment without any intervention.The PE,ME and PME are given corresponding treadmill training,enriched environment intervention or treadmill training combined with enriched environment intervention five times a week for 8 weeks.Morris water maze is used to evaluate the spatial memory of mice.Nissl staining is used to observe the neuronal damage in hippocampal CA1 region.Transmission electron microscope is used to observe the morphological changes of neurons in hippocampal CA1 region.Western Blot is used to detect the expression of hippocampal mitochondrial dynamic related proteins Mfn2,OPA1 and Drp1.Results:1.Morris water maze test results of mice in each group: in the 4-day place navigation experiment,the escape latency of mice in each group generally showed a downward trend.On the first day,compared with the OC,the latency of the ME and PME is shorter(P<0.05).On the next day,compared with the OC,the latency of the other groups is shorter(P<0.05).On the third day,compared with the OC,the latency of the mice in the YC and PME are further shortened(P<0.05).On the fourth day,compared with the OC,the latency of the other groups are further shortened(P<0.05).During the4 days,there was no significant difference between the other groups.After the platform was removed,compared with the YC,the percentage of staying time in the third quadrant of the OC decreased(P< 0.05).Compared with the OC,the percentage of staying time in the third quadrant of each intervention group increased(P< 0.05).Compared with the PE and PME,the percentage of staying time in the third quadrant of the PME group further increased(P <0.05).2.Results of Nissl staining of hippocampal CA1 region of mice in each group: In the YC,neuron cells have normal morphology,clear nucleolus,complete structure,large and numerous Nissl bodies,mottled blue-purple staining of cell bodies,and clear and pale tiger spots.In the OC,the number of nerve cells in hippocampal CA1 region decreases,cell structure is destroyed obviously,normal neurons are rare,cell atrophies,Nissl body number has decreased obviously,lysis phenomenon is obvious,vacuolated changes are observed,staining is lighter,and morphological structure is unclear.In the PE and ME,the number of neurons in hippocampal CA1 region has decreased,with fuzzy structure,uneven distribution and sparse arrangement,but the morphology of neurons is normal.PME has more neurons,clearer structure,uniform distribution,neat arrangement,normal neuron cell morphology,clear nucleolus and complete structure.3.Transmission electron microscopy results of hippocampal CA1 neuronal mitochondria in each group of mice: The YC hippocampal CA1 neuronal mitochondria is in good condition,with intact spine and no damage.In the OC,the state of neurons in hippocampal CA1 region of mice is poor,most cells are damaged,most mitochondria are seriously damaged,contents are lost,and ridges are fractured.In the PE and ME,Mitochondrial contents of some cells in hippocampal CA1 region are lost and dissolved,and a small number of mitochondria are densely stained.In the PME,mitochondria of most neurons in hippocampal CA1 region are in good condition,with intactridges,and a small number of mitochondria in cells have membrane damage phenomenon.4.Expression of Mfn2,OPA1 and Drp1 protein in hippocampus of mice in each group: Compared with the YC,the expressions of Mfn2 and OPA1 protein in the OC have decreased(P<0.05),while the expressions of Drp1 protein have increased(P<0.05),the expressions of Mfn2 and OPA1 protein in each intervention group have increased(P<0.05),while the expressions of Drp1 protein have decreased(P<0.05).Compared with the OC,the expressions of Mfn2 and OPA1 protein in each intervention group have increased(P<0.05),while the expressions of Drp1 protein have decreased(P<0.05).Compared with the PE and ME,the Mfn2 and OPA1 protein expressions in PME group have increased(P<0.05),while the Drp1 protein expressions have decreased(P<0.05).Conclusion:1.The intervention of "physical-mental exercise" can improve the spatial learning and memory of aging mice effectively,reduce neuronal damage in hippocampal CA1 region,improve the morphological structure of neuronal mitochondria,play a certain anti-aging role and the effects are better than PE or ME.2.The anti-aging effect of the intervention of "physical-mental exercise" may be realized by up-regulating the expression of Mfn2,OPA1 protein and down-regulating the expression of Drp1 protein,thus promoting the fusion and inhibiting division of neuron mitochondria in hippocampus of aging mice.