原花青素对抑郁小鼠认知功能改善的表观遗传机制

Epigenetic mechanism of proanthocyanidins in improving cognitive function of depressed mice

【目的】探索分析原花青素对抑郁小鼠认知功能改善的表观遗传学机制。【方法】采用慢性束缚应激实验建立小鼠抑郁模型,并分别使用低、中、高3 个浓度的原花青素对抑郁小鼠进行药物干预,通过跳台实验和八臂迷宫实验观察各组小鼠的认知功能,观察原花青素对抑郁小鼠认知功能的改善情况,并通过Western blotting 技术检测小鼠海马组织中脑源性神经营养因子(brain derived neurotrophic factor,BDNF)和甲基化CpG 结合蛋白2(methyl CpG-binding protein 2,MeCP2)的蛋白表达情况,分析原花青素对抑郁小鼠认知功能改善的表观遗传机制。【结果】慢性束缚应激可缩短小鼠跳台实验中的潜伏期,增加其错误次数,能够增加小鼠八臂迷宫实验中总探究时间,增加工作记忆错误和参考记忆错误的数量,并能够降低小鼠海马组织中BDNF和MeCP2 的蛋白表达,上述差异均有统计学意义(P<0.05)。低、中浓度的原花青素可以减轻慢性束缚应激引起的小鼠认知功能障碍,并提升BDNF 和MeCP2 的蛋白表达。【结论】原花青素可通过提升小鼠海马组织中MeCP2 的蛋白表达,进行表观遗传修饰,可提升记忆相关分子BDNF 的蛋白表达,改善抑郁小鼠的认知功能。

【Objective】To explore and analyze the epigenetic mechanism of proanthocyanidins in improving cognitive function of depressed mice.【Methods】The depression models of mice were established by chronic restraint stress test.The depression mice were treated with low,medium and high concentrations of proanthocyanidins.The cognitive function of mice in each group was observed by step-down test and eight-arm maze test.The improvement of cognitive function of depression mice by proanthocyanidins was observed.The expression of brainderived neurotrophic factor (BDNF) and methyl CpG-binding protein 2 (MeCP2) were detected by Western blotting.The epigenetic mechanism of proanthocyanidins in cognitive improvement of depressed mice was analyzed.【Results】Chronic restraint stress significantly shortened the latency and increased the number of errors in step-down test.It increased the total exploring time in eight-arm maze test,increased the numbers of WME and RME,and reduced the expression of BDNF and MeCP2 in the hippocampus of mice (P<0.05).Low and medium concentrations of proanthocyanidins alleviated cognitive impairment induced by chronic restraint stress in mice,and increased the protein expression of BDNF and MeCP2.【Conclusion】Proanthocyanidins can enhance the expression of memory-related molecule BDNF and improve the cognitive function of depressed mice by increasing the expression of MeCP2 in hippocampus and influencing epigenetic modification.