The Effect Of Aerobic Exercise On Ras-ERK-bcl2/bax Pathway And Learning And Memory In Prefrontal Cortex Of AD Mice

Objective: To investigate whether the 8-week aerobic exercise can reduce the apoptosis of nerve cells and improve their cognitive,abilities of learning and memory by affecting the Ras-ERK-Bcl2/Bax pathway in the prefrontal cortex of AD model mice.Methods: Forth-eight healthy male 12-week C57BL/6J mice were randomly divided into the control group(group C),the model group(group M),and the exercise model group(group E),with 16 mice in each group.The mice in the group C were intraperitoneally injected daily with 0.9% sodium chloride;The mice in the group M were intraperitoneally injected daily with D-galactose(80 mg/kg/day)and aluminum trichloride(5 mg/kg/day)for continuous 8weeks,the AD model was constructed;The mice in the group E performed the treadmill exercise while modeling according to the group M,5 times/week,60min/time.First,the mice moved at a speed of 15m/min for 10 min,then,at a speed of 18m/min for 40 min,and finally,at a speed of 15m/min for 10 min.After 8-week exercise and modeling,the Y maze and the Morris water maze were used to detect the behavioral indicators of each group of the mice;HE staining and Nissl staining of prefrontal cortical tissue sections were performed,prefrontal cortical cell morphology and neuronal apoptosis were observed separately;Immunohistochemistry and Western Blot methods were used to detect expression levels of Ras,Raf,MEK,ERK1/2,p-ERK1/2,bcl-2,bax protein in the prefrontal cortex.Results: 1.Behavioral observation: As far as the Y maze was concerned,compared with the group C,the alternating behavior of the group M was significantly reduced(P<0.01).Compared with the group M,the alternating behavior of the group E was extremely significantly increased(P<0.01);With regard to the Morris water labyrinth experiment,positioning navigation experiment found that compared with the group C,the incubation period of the group M was significantly increased on the third,fourth and fifth days(P<0.01);Compared with the group M,the incubation period of the group E was decreased on the second day(P<0.05),and all decreased on the third,fourth,and fifth days(P <0.01).The space exploration experiment found that compared with the group C,the number of mice crossing the platform in the space exploration experiment of the group M was reduced(P<0.01).Compared with the group M,the number of crossing the platform of the group E was significantly increased(P<0.05).2.HE staining observation of the morphology of the prefrontal cortex of the brain found that the prefrontal cells in the group C were full and the nucleus was clear;Compared with the group C,the cell morphology of the group M was abnormal,and the phenomenon of karyopyknosis.The number of normal cells was significantly reduced(P<0.01);Compared with the group M,the phenomenon of karyopyknosis of the group E was reduced,the morphology tended to be normal,and the number of normal cells was significantly increased(P<0.05).Nissl staining observation of neuronal cells of the prefrontal cortex of the brain found that the morphology of neuronal cells and granulosa cells in the group C mice was intact,and Nissl bodies in the cytoplasm were abundant;Some cytoplasms in the group M were autolyzed.Nissl bodies were significantly reduced;Neurons in the group E were lost.Compared with the M group,the degeneration situation was significantly improved,and the neuronal cell structure was more complete.3.Immunohistochemistry and Western Blot molecular test analysis showed that compared with the group C,the expressions of Ras and Raf of the group M were significantly reduced(P<0.01);Compared with the group M,Ras of the group E was extremely significantly increased(P<0.01),the expression of Raf was extremely significantly increased(P<0.05).The change of MEK expression among the groups was not obvious(P>0.05).Compared with the group C,the expression of p-ERK1/2 of the group M was extremely significantly decreased(P<0.01);Compared with the group M,the expression of p-ERK1/2 of the group E was significantly increased(P<0.05).There was no significant difference in the expressions of ERK1/2 among the groups(P>0.05).Western Blot method was used to detect the expression of Bcl-2/Bax.Compared with the group C,the expression of bcl-2 of the group M was extremely significantly decreased(P<0.01),and the expression of Bax was extremely significantly increased(P<0.01).Compared with the group M,the expression of Bcl-2 of the group E was significantly increased(P<0.05),and the expression of Bax was extremely significantly decreased(P<0.01).Conclusions:1.Behavioral results suggest that 8-week intraperitoneal injection of D-galactose and aluminum trichloride can reduce the learning and memory abilities of AD mice,and 8-week aerobic exercise can alleviate the decline of learning and memory abilities of AD model mice.2.Morphology study shows that 8-week aerobic exercise can reduce the cell morphologyand structure damage of prefrontal cortex,reduce neuronal apoptosis,and have a neuroprotective effect on AD mice.3.Molecular mechanism analysis shows that 8-week aerobic exercise can activate the Ras-ERK pathway of the prefrontal cortex,increase the expression of p-ERK1/2 protein,up-regulate the expression of bcl-2,inhibit the expression of bax,and reduce neuronal apoptosis of AD mice.