Effects Of Exercise Activated Autophagy Related Signaling Pathway On Alzheimer’s Disease Model Rats

Objective: At present, China has entered the aging society, aging and aging related diseases have become one of the major issues facing the country and society. Alzheimer’s disease(AD), also known as senile dementia, is a mostly occurs in the elderly, of cognitive impairment and memory ability damage as the main clinical symptoms of nervous system degenerative diseases, with the acceleration of population aging process, AD incidence rate assumes the trend of escalation obviously, suitable for movement of the load is considered to be an effective strategy for non drug intervention ad. In recent years, a new kind of cell death mode of autophagy has attracted widely attention. By autophagy pathway can degradation dysfunction of organelles and / or abnormally folded proteins, play an important role in maintaining cellular homeostasis. However, there is little research on the current study of the autophagy pathway in AD neurons. The mechanism needs to be further clarified. This study intends to explore the long-term moderate load motor stimulation of injection of D-galactose induced AD model rats learning and memory influence and hippocampal neuronal autophagy related signaling pathways and molecular mechanisms, as the research to explore the AD pathogenesis and treatment options of opening up new ideas.Methods: This study selected two month old male SD rats as the research object, before the experiment, SD rats were randomly divided into 4 groups, namely normal control group(NC group, normal control group), exercise control group(EC group, exercise control group), ad model group(AD control group AC group), ad model training group(Alzheimer’s exercise group and AE group), 20 rats in each group. NC group according to conventional breeding, free activities, daily morning intraperitoneal injection of a saline(150 mg / kg), a total of 8 weeks; AC group according to conventional feeding, free activities, daily morning intraperitoneal injection of 1 D- galactose(150 mg / kg), a total of 8 weeks; group of AE in addition to the daily by intraperitoneal injection of D-galactose(150 mg / kg), treadmill training for 8 weeks. Rats were trained to: 1 week running speed of 10 m / min, 30 min / D, 6D / W for, Sunday rest; at 2-4 weeks running speed 15 m / min, 45min/d, 6D / W for, Sunday rest; the 5-8 week run speed 15 m / min, 60 min / D, 6D / W for, Sunday rest; EC group training program with the AE group and continues for 8 weeks. After the end of the experiment, by Morris water maze test in each group of rats learning and memory ability; Nissl staining was detected in the hippocampus neuron survival state; Golgi method to detect the hippocampal neuronal dendritic spine density; immunofluorescence staining detection of phosphorylated AMPK expression; chemical colorimetry to detect hippocampal tissue superoxide dismutase(SOD) activity, malondialdehyde(MDA) content and glutathione peroxidase(GSH) content; Western blot was used to detect the p-ampk, lc3 i,lc3ii, beclin-1, p-Akt, bcl-2 expression. SPSS13.0 software was used for statistical analysis, all data were expressed, the two groups of data were compared using t test, multiple groups were compared using ANOVA, P<0. 05 for the difference was statistically significant.Results: the experimental results showed that the escape latency of Morris water maze in each group decreased with the increase of the experimental time. In experiment third, 4, 5 days, AC group and AE group escape latency compared with NC group, significantly increased(p<0.05, p<0.01). On the fifth day of the experiment, the escape latency of AE group was significantly lower than that of AC group(p<0.01). Compared with the NC group, the AC group in the target quadrant of the stay time was significantly reduced(p<0.01), the number of times through the original platform also significantly reduced(p<0.01), which shows that the space exploration ability of AC group was significantly reduced compared with the NC group. Compared with the AC group, the AE group was significantly longer(p<0.05) in the target quadrant, and the number of crossing the original platform was significantly increased(p<0.01). Nissle staining showed, NC group and EC group of neurons in the brain is full, clear cell boundary, tightly packed cells; AC group of neurons arranged in a sparse, fuzzy boundary cells, massive pyknotic nuclei appear; AE group neurons nucleus also appeared pyknosis, but cells arranged more clear and tight. Expression of activated neurons of rats significantly reduced the number of Golgi staining results show that the AC group in hippocampal neurons of the contralateral dendrites than in the NC group(P < 0.01), but the AE group on the lateral dendrite number compared with the AC group and NC increased significantly(P < 0.01, P < 0.05); immunofluorescence staining showed that AE group hippocampus p-ampk; enzyme activity assay results show that AE group of hippocampal tissue SOD activity was significantly increased(P < 0.01), MDA content was significantly decreased(P < 0.01), but the activity of GSH had no significant difference(P > 0.05). Western blot results showed that with the NC group, the AC group of p-ampk protein expression was significantly decreased(P < 0.01), AE group of p-ampk expression compared with NC group and AC group significantly increased(P < 0.01). The ratio of LC3II/LC3 I in group AE was significantly higher than that in group NC and group AC(p<0.01), and there was no significant difference in the ratio of LC3II/LC3 I in the other three groups. Compared with the NC group, EC group and AE group Beclin-1 protein expression was significantly enhanced(p<0.01), AC group Beclin-1 protein expression was significantly lower(p<0.01); compared with the AC group, AE group Beclin-1 protein expression was significantly enhanced(p<0.01). Compared with the AC group, the expression of P-Akt and Bcl-2 protein in AE group was significantly increased.Conclusions:(1) 8 weeks of treadmill exercise can significantly improve the learning and memory ability of AD rats, increase the number of neurons in hippocampal CAI region and reduce injury of AD rat hippocampal neurons and dendritic density are closely related.(2) 8 weeks of treadmill exercise can activate AD neurons in rats with phosphorylated AMPK expression, thereby causing neuronal autophagy, autophagy is the marker protein LC3 and Beclin-1 expression in hippocampal neurons increased significantly.(3) 8 weeks of treadmill exercise can improve the SOD rat hippocampus AD activity, reduce the deposition of MDA so as to protect the neurons in AD rats.(4) 8 weeks of treadmill exercise can improve the expression of Akt\Bcl-2 signaling pathway, which promotes neuronal survival.