Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats
Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats
复制标题
胱硫醚-β-合酶衍生的硫化氢是大鼠杏仁核长期增强和提示恐惧记忆所必需的。
DOI：
10.1016/j.pbb.2017.03.002
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发表时间：
2017-04-01
影响因子：
3.6
通讯作者：
Yang, Yuan-Jian
中科院分区：
文献类型：
--
作者：
Chen, Hai-Bo;Wu, Wen-Ning;Yang, Yuan-Jian
硫化氢（H2S）是一种内源性气体分子，在大脑中起到神经调节剂的作用。我们以前报道过H2S调节大鼠杏仁核突触可塑性并提示恐惧记忆。然而，内源性H2S是否是杏仁核长时程增强（LTP）诱导和线索恐惧记忆形成所必需的尚不清楚。在这里，我们表明，胱硫醚-β-合酶（CBS），主要的H2S产生酶在大脑中，在大鼠杏仁核中高度表达。通过抑制剂抑制CBS活性防止了外侧杏仁核（LA）区域中H2S的活性触发生成。脑片与CBS抑制剂孵育显著阻止了丘脑-LA通路中NMDA受体（NMDARs）依赖性LTP的诱导，并且LA内灌注CBS抑制剂损害了大鼠的线索恐惧记忆。值得注意的是，用H2S供体而不是CBS激活剂处理显著逆转了由CBS抑制引起的LTP和恐惧记忆的损伤。机制上，CBS活性的抑制导致丘脑-LA通路中NMDAR介导的突触反应减少，并且用H2S供体处理恢复了NMDAR的功能。总之，这些结果表明，CBS-derived H2S是必需的杏仁核突触可塑性和线索的恐惧记忆在大鼠，和内源性H2S的影响可能涉及NMDAR功能的调节。(C)2017爱思唯尔公司All rights reserved.
Hydrogen sulfide (H2S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H2S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H2S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-beta-synthase (CBS), the predominant H2S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H2S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H2S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H2S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H2S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H2S might involve the regulation of NMDAR function. (C) 2017 Elsevier Inc. All rights reserved.