Institutional Repository, Institute of Psychology, Chinese Academy of Sciences
|其他题名||The effects of different stressors on behavior, protein levels and phosphorylation of Neurogranin in rats|
|关键词||情绪应激 生理应激 神经颗粒素 海马 前脑皮层 焦虑 抑郁|
|摘要||为探讨应激所致行为效应的脑机制，本研究考察了急慢性生理应激和情绪应激对大鼠行为和脑内神经颗粒素（Neurogranin，NG）水平影响的差异，以及大鼠脑内NG改变与其行为方式变化之间的相互关系。研究采用急、慢性强迫性冷水游泳作为生理应激和不确定性无水空瓶刺激作为情绪应激模型，以旷场实验、高架十字迷宫任务和糖精水测试评定大鼠应激后的行为变化，以Western blotting方法测定大鼠海马、前脑皮层的NG蛋白含量和磷酸化水平，并分析两者之间的相互关系。以免疫组化方法对海马CA1-CA3区和前脑皮层M1-M2区的NG蛋白阳性表达的情况进行观察，主要实验结果如下：1.慢性生理应激引起大鼠的活动量和修饰行为显著增加，糖精水摄入量减少；海马和前脑皮层区域的NG含量显著下降，并且NG水平与修饰、探究和直立等多项行为指标呈显著负相关2.慢性情绪应激引起大鼠的修饰行为显著增加；前脑皮层的NG含量显著下降；前脑皮层的NG水平与修饰行为呈显著负相关3.慢性游泳应激使大鼠海马CA1-CA3区域、前脑皮层M1-M2区域的NG表达均明显减弱；而慢性情绪应激使大鼠前脑皮层M1-M2区的NG表达明显减弱4.急性生理应激引起大鼠明显的呆滞行为；海马和前脑皮层区域的NG含量以及NG磷酸化水平显著增加；前脑皮层的NG磷酸化水平与呆滞行为呈显著正相关5.急性情绪应激引起大鼠的水平活动量显著增加；海马和前脑皮层的NG磷酸化水平显著增高；海马的NG磷酸化水平与水平活动量呈显著正相关 上述结果表明，急慢性生理应激和情绪应激能引起大鼠不同的行为异常。在相同时程的情绪应激和生理应激作用下，脑内的NG含量和磷酸化水平呈相同的变化趋势。而急性应激和慢性应激对脑内的NG含量和磷酸化水平的影响则存在差异。并且NG的水平与行为异常的发生相关显著。不同时程、不同性质的应激源所致行为障碍的差异涉及到共同和特异性的中枢机制。提示NG是预测应激所致焦虑或抑郁行为的敏感生物学指标，可能是参与应激所致行为障碍的中枢机制重要的物质分子。|
The aim of this study was to investigate the effects of different stressors on behaviors, protein levels and phosphorylation of neurogranin (NG), and the possible role of NG involving in the brain mechanisms underlying stress-induced behavioral changes. In the study, physiological stress (PS) was induced by forced cold water (10℃) swimming, and emotional stress (ES)was induced by randomly giving empty water bottles to rats trained to drink water at set times. Behavioral changes in rats after stress were investigated by using open-field test, elevated plus maze task and sucrose preference test. Protein levels and phosphorylation of NG of hippocampus and frontal cortex were determined by Western blotting. The expression of NG in hippocampal CA1-CA3 regions and frontal cortex M1-M2 regions were determined by immunohistochemistry method. The main results are as the follows:
1. Chronic forced cold water swimming stress significantly increased behavioral activity and grooming in open field test and induced a reduction in the volume of consumed sucrose. The NG levels of both hippocampus and frontal cortex were significantly decreased, and phosphorylation of NG was not detected. Most of behaviors, including grooming, exploration and rearing, were negatively correlated with the level of NG.
2. Chronic emotional stress significantly increased grooming behavior of rats. The NG levels of frontal cortex were significantly decreased, and phosphorylation of NG was also not detected. The NG levels of frontal cortex were negatively correlated with grooming behavior.3. After chronic physiological stress, NG expression that was observed in hippocampal CA1-CA3 regions and frontal cortex M1-M2 regions was significantly decreased. Chronic emotional stress also resulted in decrease in NG expression in frontal cortex M1-M2 regions.4. Acute cold water swimming stress induced obvious freezing behavior of rats. Both the protein levels and phosphorylation of NG in hippocampus and frontal cortex were significantly increased. The positive correlation is significant between phosphorylation of NG in frontal cortex and freezing behavior.5. Acute emotional stress significantly increased locomotor activity of rats. The phosphorylation of NG in hippocampus and frontal cortex was also significant increased. The positive correlation is significant between phosphorylation of NG in hippocampus and locomotor activity. In conclusion, acute stress and chronic stress have different effects on behavior, protein levels and phosphorylation of NG. Almost all of the behaviors changed were significantly correlated with the protein levels and/or phosphorylation of NG in brain. The central mechanisms underlying behavioral changes induced by acute stress and chronic stress are not the same. NG may be involved in the central mechanisms underlying different stress-induced behavioral disorders, and could be a sensitive predictor of anxiogenic effect of stress.
|李欢欢. 不同应激源对大鼠行为的影响及其脑内神经颗粒素变化差异[D]. 北京. 中国科学院研究生院,2005.|