摘要
目的探讨运动干预对慢性应激模型大鼠抑郁行为及不同脑区细胞外信号调节蛋白激酶(ERK)-环磷酸腺苷反应元件结合蛋白(CREB)信号通路磷酸化水平变化。方法 40只雄性SD大鼠随机分为对照组、应激组、运动组、运动+应激组,采用慢性温和不可预知性应激方法建立抑郁症模型;采用旷场实验及糖水消耗实验进行行为学测定,免疫组织化学方法检测海马、额叶皮层磷酸化ERK(p-ERK)及磷酸化CREB(p-CREB)表达变化。结果与对照组比较,慢性应激大鼠水平运动评分[(20.4±11.67)分]、垂直运动评分[(5.4±2.36)分]、体重增加量[(29.82±17.68)g]和糖水摄入量[(8.13±2.56)g]均减少(P<0.01),海马、额叶皮层p-ERK[(6.15±2.86)、(12.43±5.14)]及p-CREB[(2.89±0.51)、(2.34±0.53)]表达均降低(P<0.01);与应激组比较,运动+应激组大鼠水平运动评分[(48.2±22.66)分]、垂直运动评分[(13.1±3.06)分]、体重增加量[(76.50±25.81)g]和糖水摄入量[(17.02±4.13)g]均升高;与对照组比较,运动组各脑区P-ERK/P-CREB[(23.76±4.11)、(32.64±5.37)、(6.73±0.55)、(5.79±0.51)]磷酸化水平均升高(P<0.05)。结论运动具有一定抗抑郁样行为学效应,其分子机制可能与上调脑内ERK/CREB信号通路的磷酸化水平有关。
Objective To explore effects of exercise on depressive-like behavior and the phosphorylation level of extracellular signal-regulated protein kinase(ERK)-cAMP response element binding protein( CREB ) signal pathway in different cerebral regions of rats under chronic unpredictable mild stress (CUMS). Methods Forty male Sprague Dawley rats were randomly divided into 4 groups : control group, stress group, exercise plus stress group, and exercise group. The rat model of depression was made by the method of chronic unpredictable mild stress. Exercise model was established with voluntary wheel running. The open field test and sucrose preference test was utilized to determine the depressive-like behavior. Phosphorylated ERK and CREB in the frontal cortex and hippocampus were examined with immunohistochem- istry. Results Compared with the rats of control group, chronic-stressed rats showed significantly decreased number of crossing square (20. 4 ± 11.67), times of rearing ( 5.4 ± 2. 36 ) and sucrose consumption ( 8. 13 ±2. 56 g, P 〈 0. 01 ). The p-ERK and p-CREB expressions in hippocampus (6. 15 ± 2. 86,2. 89 ± 0. 51 ) and frontal cortex ( 12. 43 ±5. 14,2. 34 ±0. 53 ) were also significantly decreased in stress group( P 〈 0. 01 ). Compared with stress group, exercise significantly diminished the number of crossing square, times of rearing, and body weight of the rats (48. 2 ±22. 66,13.1 ±3.06,17.02 ±4. 13 g) induced by chronic stress and increased the levels of p-ERK and p-CREB in hippocampus ( 14. 95 ±3.54,4. 47 ±0. 45 ) and frontal cortex ( 23.57 ±4. 76,3.87 ±0.44 ) ( P 〈 0. 05 for all). Compared with those in control group, the phosphoryl- ation levels of ERK and CREB in the two cerebral regions (23.76 ±4. 11,32. 64 ±5.37,6. 73 ±0. 55,5.79 ±0. 51 ) were higher in exercise group (P 〈 0. 05 for all). Conclusion Exercise has certain antidepressant behavior effect, and its molecular mechanism may be associated with up-regulation of phosphorylation levels of ERK-CREB signaling pathway in brain.
出处
《中国公共卫生》
CAS
CSCD
北大核心
2013年第3期368-370,共3页
Chinese Journal of Public Health
基金
四川省科技厅青年基金(09ZQ026-078)
四川省教育厅资助项目(10ZC060)
四川省科技厅项目(2010JY0140)