可可碱抗慢性不可预知温和应激负荷致小鼠抑郁症作用研究
首发时间:2019-11-21
摘要:目的:利用慢性不可预知温和应激(CUMS)负荷小鼠模型,研究可可碱(theobriomine, Tb)对CUMS所致小鼠行为学以及神经再生和突触的影响。方法:采用多种应激因子建立CUMS激负荷小鼠模型,以自主活动、糖水偏好以及悬尾实验评价可可碱对应激小鼠行为学的影响;采用免疫组化方法考察可可碱对CUMS小鼠海马及大脑皮层神经元增殖的影响;Western blotting 法检测可可碱对小鼠海马组织中synapsin-1以及突触后致密蛋白(Postsynaptic density protein of 95kDa,PSD95)蛋白水平;ELISA法测定小鼠海马组织中BDNF水平。结果:CUMS导致小鼠表现出兴趣缺乏、绝望等抑郁样行为,给予可可碱可提高小鼠自主活动水平,增加小鼠糖水消耗量。进一步研究表明,可可碱可改善应激导致的BrdU阳性细胞数量降低以及突触蛋白synapsin-1和PSD95水平低下,提高BDNF水平,促进CREB磷酸化。结论:可可碱一定程度上能改善CUMS导致的小鼠抑郁行为,其作用机制可能与提高BDNF水平,进而促进神经元增殖,提高突触蛋白水平有关。
关键词: 慢性不可预知温和应激 可可碱 神经元增殖 突触损伤
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The antidepressant effect of theobromine on chronic unpredictable mild stress mice.
Abstract:Objective: To observe the antidepressant effect of theobromine on chronic unpredictable mild stress mice. Methods: Kunming mice were exposed to CUMS for 28 days, the administration of theobromine started after 7 days and lasted 21 days. Behavioral tests were carried out by different testing methods. Immunochemistry method was used to detect the proliferation of neurons in hippocampus cortex. The change of synapsin-1 and PSD95 were tested by Western blotting. The level of BDNF was measured by ELISA. Results: Results showed that CUMS caused significant change of behavior and decreased the proliferation of neurons and synaptic proteins in hippocampus and cortex. Treatment with theobromine improved the depressed behavior and increased the neuron proliferation and the level of synaptic proteins. Conclusions: Theobromine possessed anti-depression effect by upping the level of BDNF and increasing neuron proliferation and synaptic proteins.
Keywords: Chronic unpredicted mild stress theobromine neuron proliferation synapse injury
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