| Purpose: The current aging population is becoming increasingly prominent and agingrelated cognitive dysfunction has become one of the major factors threatening public health,while impaired hippocampal neurogenesis is the main cause of memory cognitive decline during aging.The aim of this paper is to investigate the effects of 12 weeks of aerobic exercise on neurogenesis and cognitive performance in naturally aging mice and the related molecular mechanisms.Methods: 8-week-old C57BL/6 male mice were divided randomly in two groups:young control group(Y)and young exercise group(YE),and 19-month-old mice were randomly divided into two other groups: aging control group(A)and aging exercise group(AE).The YE and AE groups were scheduled for 12 weeks of animal treadmill exercise with the following exercise regimen: exercise speed: 14m/min,exercise time.30 min,exercise incline: 6%.At the end of the exercise intervention,a 5-day Morris water maze was performed to test cognitive ability;5-bromodeoxyuridine(Brdu)was injected intraperitoneally at a dose of 50 mg/kg twice daily at 12-h intervals for 3d.The neurogenesis of the hippocampal dentate gyrus was detected by immunofluorescence staining;real-time fluorescence quantitative PCR was performed to observe the m RNA expression levels of neuron-related genes doublecortin(DCX)and neuronal nucleus(Neu N),glial cell-related gene glial fibrillary acidic protein(GFAP)m RNA expression levels,and Notch signaling pathway-related m RNA expression levels;protein immunoblotting was performed to detect the expression levels of Jag1,Hey2,Hey1 and Hes1,proteins related to Notch signaling pathway.Results:(1)The water maze test revealed that the aging mice in group A had increased escape latency time(P<0.01)and decreased swimming time in the target quadrant(P<0.01)and significantly decreased the number of times they crossed the area where the platform was located(P<0.01)compared to group Y.Compared with group A,the escape latency time decreased in the AE group after aerobic exercise intervention(P<0.01),and the time spent swimming in the target quadrant and the number of times crossing the platform area were found to be significantly higher in this group(P<0.05).(2)Immunofluorescence staining revealed that the mean optical density of Brdu+ and DCX+ cells in group A was lower than that in group Y(P<0.05),the expression of DCX and Neu N m RNA was significantly reduced(P<0.01),and the expression of GFAP m RNA was significantly higher than that in group Y(P<0.05);the mean optical density of Brdu+and DCX+ cells in group AE after aerobic exercise workout and the expression levels of DCX m RNA and Neu N m RNA expression levels were significantly higher in the AE group than in the A group(P<0.05),and a decrease in GFAP m RNA expression level also occurred(P<0.05).(3)Compared with group Y,the expression level of miR-153 was significantly lower in group A(P<0.01);after aerobic exercise intervention,the expression level of miR-153 was significantly upregulated in group AE(P<0.05).(4)Compared with group Y,group A had increased expression of Jag1,Hey2,Hey1,and Hes1,key proteins of the Notch signaling pathway(P<0.01),and upregulated expression levels of Hes1 and Hey1 m RNA(P<0.05);after the running table exercise intervention,group AE had downregulated expression of Jag1,Hey2,Hey1,and Hes1 proteins compared with group A(P <0.05),and Hes1,Hey1 m RNA expression levels were reduced(P<0.05).Conclusion:(1)Aerobic exercise intervention may increase neuron-related genes and inhibit glial cell-related gene expression,thereby reversing the aging-related reduction in neurogenesis and improving cognitive performance.(2)Twelve weeks of aerobic exercise may increase neurogenesis in aging mice by upregulating miR-153 expression and inhibiting the activation of its downstream Notch signaling pathway,ultimately improving cognitive dysfunction during aging. |
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