丰富环境对抑郁大鼠行为学及海马CA1区脑源性神经营养因子、酪氨酸激酶受体B蛋白表达的影响

Effects of enriched environment on behavior and protein expression of brain-derived neurotrophic factor and tyrosine kinase receptor B in hippocampal CA1 region of depressed rats

目的:观察丰富环境对抑郁大鼠行为学、海马CA1区脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)蛋白表达的影响。方法:实验大鼠30只,通过基线行为学测试剔除异常行为学指标的大鼠后,随机分为空白组、模型组及丰富环境组,每组8只。采用慢性温和不可预知应激建立抑郁模型,空白组及模型组不予干预,丰富环境组在应激21天后给予丰富环境干预。干预21天后采用糖水偏爱实验、旷场实验、强迫游泳实验检测大鼠抑郁样行为;HE染色、免疫组化染色法、免疫蛋白印迹法观察海马CA1区神经元形态及BDNF、TrkB蛋白表达的情况。结果:慢性应激可导致大鼠体重增长缓慢,糖水偏爱率下降,旷场内运动总距离、中心区活动距离及停留时间降低,游泳不动时间增加(P<0.01),海马CA1区BDNF、TrkB表达下降(P<0.05),提示抑郁模型建立。与模型组相比,丰富环境组大鼠糖水偏爱率升高,游泳不动时间下降(P<0.01),旷场内运动总距离、中心区活动距离及停留时间(P<0.05)均增加,海马CA1区神经元数量减少、胞体固缩破碎明显改善,BDNF、TrkB含量明显升高(P<0.05)。结论:丰富环境能够改善慢性应激导致的抑郁样行为,其机制可能与促进海马区BDNF、TrkB的表达有关。

Objective:To observe the effects of enriched environment on behavior and protein expression of brain-derived neurotrophic factor(BDNF) and tyrosine kinase receptor B(Trk B) in hippocampal CA1 region of depressed rats.Method:Thirty experimental rats were randomly divided into blank group, model group and enriched environment group after the rats with abnormal behavior indexes were eliminated through baseline behavior test, with 8 rats in each group. The depression model was established by chronic mild unpredictable stress. The blank group and model group did not being intervened,while the enriched environment group was given enriched environment intervention after 21 days of stress. After 21 days of intervention,the depression-like behavior of rats was detected by sugar water preference test,open field test and forced swimming test,and the morphology of neurons in hippocampal CA1 region and the expression of BDNF and Trk B protein were observed by HE staining,immunohistochemical staining and Western Blot.Result:Chronic stress could lead to slow growth of body weight,decrease of sugar preference rate,decrease of total exercise distance,central activity distance and residence time in open field,and increase of swimming immobility time(P<0.01), the expression of BDNF and Trk B in the hippocampal CA1 region decreased(P<0.05). Those suggested the establishment of depression model. Compared with the model group,the sugar water preference rate of rats in the enriched environment group increased, the swimming immobility time decreased(P<0.01),and the total distance of exercise in the open field,the distance of movement in the central area and stay time increased(P<0.05),the number of neurons in the hippocampal CA1 region of the rats decreased, and the pyknosis and fragmentation of the cell bodies were significantly improved, and the contents of BDNF and Trk B were increased significantly(P<0.05).Conclusion:Enriched environment can improve depression-like behavior induced by chronic stress, and its mechanism may be related to promoting the expression of BDNF and Trk B in hippocampus.