大鼠内侧前额叶皮质内ERK1/2 活化参与脊髓损伤后抑郁情绪

目的:观察细胞外信号调节激酶1/2(ERK1/2)的活化在脊髓损伤引起抑郁中的作用。方法:应用Western blot和行为药理学方法,观察脊髓损伤后(SCI)大鼠内侧前额叶皮质内(mPFC)ERK1/2及磷酸化-ERK1/2(p-ERK1/2)的表达情况及ERK1/2磷酸化抑制剂U0126对抑郁样行为的影响。结果:脊髓损伤后的第2天到第8周,SCI模型大鼠的BBB评分均显著低于假手术组,差异具有统计学意义(p0.05)。脊髓损伤后8周-12周,SCI模型大鼠强迫游泳不动时间与假手术组相比明显缩短,mPFC内pERK1/2蛋白表达水平明显升高,总ERK 1/2的蛋白水平则未见组间差异,而给予U0126的大鼠的不动时间与给药之前相比明显延长增加,mPFC内pERK1/2蛋白表达水平较SCI模型大鼠明显降低,差异均具有统计学意义(P0.05)。结论:内侧前额叶皮质内ERK1/2的激活参与了脊髓损伤后引起的突触可塑性,在相关的抑郁样行为的产生中发挥了重要的作用。

Activation of Extracellular Signal-Regulated Kinase1/2 in the Medial Prefrontal Cortex Contributes to Spinal Cord Injury-Induced Depression

Objective:To observe the activation of extracellular singal-regulated kinase1/2 (ERK1/2) on the spinal cord injury-induced depression.Methods:Western blot and behavioral methods were used to investigate the effect of extracellular signal-regulated kinase1/ 2(ERK1/2) activation on the spinal cord injury (SCI) in the medial prefrontal cortex (mPFC), and the effect of inhibiting ERK1/2 phosphorylation by microinjection of U0126 into the mPFC on the depression-like behavior.Results:Fromthe first 2 days to the 8 weeks after spinal cord injury, the BBB scores of SCI rats was significantly lower than the control group (P<0.05). In 8-12 weeks after spinal cord injury, the fixed time of forced swimming test in SCI rats was significantly shorter than the control group, the level of pERK1/2 in the mPFC was upregulated in the SCI rats compared with control rats, not significant difference was found in the total level of ERK 1/2 between different groups, while after U0126 administration, the fixed time was significantly prolonged, the level pERK1/2 in the mPFC was significantly decreased (P<0.05).Conclusion:The activation of ERK1/2 in the mPFC might contribute to the process of SCI-induced synaptic plasticity, which played an important role in the depression-like behavior.