A Possible Link Between HCN Channels and Depression.
A Possible Link Between HCN Channels and Depression.
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HCN 通道与抑郁症之间的可能联系
DOI：
10.1177/2470547018787781
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Johnston D
中科院分区：
文献类型：
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作者：
Kim CS;Johnston D
越来越多的证据表明，超极化激活的环核苷酸门控非选择性阳离子（HCN）通道和抑郁症之间可能存在联系。在最近发表在《分子精神病学》上的一项研究中，我们首次证明了慢性应激后，Ih（HCN通道介导的膜电流）和HCN 1蛋白表达在背侧而非腹侧CA 1区增加，而急性应激后则没有。Ih的这种上调仅限于CA 1神经元的体周区域，并导致神经元兴奋性的降低。在慢性不可预测的应激诱导的抑郁症发生前，背侧CA 1区HCN 1蛋白表达的减少足以提供对慢性不可预测的应激的弹性效应。此外，在体内阻断肌质/内质网Ca 2 +-ATP酶（SERCA）泵，已知增加细胞内钙水平和上调Ih的操作，产生类似于焦虑的行为和Ih的增加，类似于慢性不可预测的抑郁症应激模型中观察到的。在这里，我们分享我们的观点：（1）在抑郁症的发展过程中，HCN 1通道的功能和表达如何以亚细胞区域特异性的方式在大脑中发生变化，以及（2）HCN 1蛋白表达的减少如何提供对慢性压力的恢复力。
Growing evidence suggests a possible link between hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels and depression. In a recent study published in Molecular Psychiatry, we first demonstrate that Ih (the membrane current mediated by HCN channels) and HCN1 protein expression were increased in dorsal, but not in ventral, CA1 region following chronic, but not acute stress. This upregulation of Ih was restricted to the perisomatic region of CA1 neurons and contributed to a reduction of neuronal excitability. A reduction of HCN1 protein expression in dorsal CA1 region before the onset of chronic unpredictable stress-induced depression was sufficient to provide resilient effects to chronic unpredictable stress. Furthermore, in vivo block of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pumps, a manipulation known to increase intracellular calcium levels and upregulate Ih, produced anxiogenic-like behavior and an increase in Ih, similar to that observed in chronic unpredictable stress model of depression. Here, we share our view on (1) how the function and expression of HCN1 channels are changed in the brain in a subcellular region-specific manner during the development of depression and (2) how a reduction of HCN1 protein expression provides resilience to chronic stress.