Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels.
Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels.
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DOI：
10.1002/hipo.22052
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发表时间：
2013-01
期刊：
影响因子：
3.5
通讯作者：
Pozzo-Miller, Lucas
中科院分区：
文献类型：
--
作者：
Leuner, Kristina;Li, Wei;Amaral, Michelle D.;Rudolph, Stephanie;Calfa, Gaston;Schuwald, Anita M.;Harteneck, Christian;Inoue, Takafumi;Pozzo-Miller, Lucas
关键词：
圣约翰草的标准提取物(贯叶连翘)通常用于治疗轻度到中度的抑郁症。其活性成分是金丝桃素，这是一种间苯三酚衍生物，通过激活非选择性阳离子TRPC6通道增加细胞内Na+浓度，减少5-羟色胺和去甲肾上腺素的重新摄取。TRPC6通道也是钙离子渗透性的，导致细胞内钙离子升高。事实上，金丝桃素激活了TRPC6介导的电流和大鼠PC12细胞中的钙瞬变，从而诱导其分化，模拟了NGF的神经营养作用。在这里，我们发现金丝桃素通过激活TRPC6通道来调节培养的海马片CA1和CA3锥体神经元的树突棘形态。金丝桃素还可诱发细胞内钙瞬变和去极化内向电流，对TRPC通道阻断剂La3+敏感，从而类似于神经营养素BDNF在海马锥体神经元中的作用。这些结果表明，圣约翰麦芽汁的抗抑郁作用是由与BDNF相似的机制介导的。
The standardized extract of the St. John’s wort plant (Hypericum perforatum) is commonly used to treat mild to moderate depression. Its active constituent is hyperforin, a phloroglucinol derivative that reduces the reuptake of serotonin and norepinephrine by increasing intracellular Na+ concentration through the activation of non-selective cationic TRPC6 channels. TRPC6 channels are also Ca2+-permeable, resulting in intracellular Ca2+ elevations. Indeed, hyperforin activates TRPC6-mediated currents and Ca2+ transients in rat PC12 cells, which induce their differentiation, mimicking the neurotrophic effect of NGF. Here, we show that hyperforin modulates dendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampal slice cultures through the activation of TRPC6 channels. Hyperforin also evoked intracellular Ca2+ transients and depolarizing inward currents sensitive to the TRPC channel blocker La3+, thus resembling the actions of the neurotrophin BDNF in hippocampal pyramidal neurons. These results suggest that the antidepressant actions of St. John’s wort are mediated by a mechanism similar to that engaged by BDNF.
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影响因子：
3.6
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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