摘要
目的研究精神应激后部分脑区内BDNF、CREB蛋白表达的时序性变化,进一步探讨BDNF对精神应激的保护作用及其机制。方法采用旁观电击大鼠应激模型作为精神应激模型,利用免疫组织化学技术,观察精神应激后海马CA1区、前额叶皮质、杏仁核中央核、伏隔核(壳区)、中脑导水管周围灰质、腹侧背盖区等脑区内BDNF、CREB蛋白不同时点的表达。结果 1)精神应激后即刻各脑区BDNF表达明显下调,灰度值明显大于对照组,差异具有极显著性;精神应激后0.5h、1hBDNF表达开始恢复,但仍少于对照组,差异有显著性;精神应激后2hBDNF表达除VTA区外,其余各脑区恢复至对照组水平,两组比较无明显差异;精神应激后6hBDNF表达继续增高,明显高于对照组(VTA区除外),差异有显著性;精神应激后24hBDNF mRNA表达达最高值,明显高于对照组,差异有显著性(VTA区除外,VTA区表达仍低于对照组)。2)应激后即刻,精神应激组P-CREB表达较对照组明显减少,差异具有显著性;随后二者表达逐渐增多,精神应激后24h时,精神应激组P-CREB表达较对照组明显增多。3)精神应激后即刻、精神应激后24h各对应脑区BDNF蛋白与P-CREB灰度值明显相关(P均<0.05),二者存在明显时空相关性。结论旁观电击大鼠应激模型能产生明显的精神应激;BDNF参与了机体精神应激状态下的"异稳态平衡",对精神应激有明显保护作用;BDNF的保护作用可能是通过CREB路径实现的。
Objective To study the dynamic changes of brain-derived neurotrophic factor （BDNF） and cAMP response element binding protein （CREB） gene expression after acute mental stress in some brain regions of rats in order to explore the protective effects and mechanisms of BDNF in mental stress. Methods We applied the Communication Box to establish animal model of mental stress and measure the expression of both BDNF and CREB in their CA1 of hippocampus, prefrontal cortex （PF）, central amygdaloid nuclei （AG）, shell of accumbens nucleus （NAC）,periaqued-uctal gray （PAG）,ventral tegmental area（VTA） and Dorsomedial hypothalamic nucleus （DM） u- sing immunohistochemistry methods. Results 1 ）The gray intensity of BDNF protein in the brain regions men- tioned above of mental stress group were very significantly higher than that of control group, indicating significant- ly decreased expression of BDNF protein, at 0.5h and lh after mental stress. However, there were no significant difference of BDNF protein in almost regions （other than the BDNF mRNA in VTA region） between mental stress group and control group at 2h following mental stress, and mental stress group still decreased relative to that in control group. BDNF protein at 0.5h and lh higher than at 0 h in mental stressed animals. These findings revealed gradual recovery of BDNF during 2 hours following mental stress in the experimental animals. What,s more, the ex- pression of BDNF protein obviously increased at 6h following mental stress （other than in VTA region） and reached a strikingly higher level tested at 24h following stress （also other than in VTA region） compared with the control group. Specially,in contrast to other brain regions, VTA region expressed still lowered BDNF but incongruently higher BDNF protein at 24h following mental stress. 2）At the Oh after stress, the expression of P-CREB in mental stress group were significantly decreased than in control group, but at the 24h, they were both significantly in- creased to a level significantly higher than that in the control group. 3）The gray intensity of BDNF and that of P-CREB were significantly correlated with each other at both Oh and 24h after stress,implying certain spatio-tempo- ral association between the BDNF and CREB. Conclusion The Communication Box model can induce obvious men- tal stress,and BDNF can bring about protective effects on mental stress, which were involved in the heterho- meostasis of mental stress. The protective effects of BDNF may be through CREB pathway.
出处
《济宁医学院学报》
2013年第2期84-88,共5页
Journal of Jining Medical University
