Chen Hai-Bo, Wu Wen-Ning, Wang Wei, Gu Xun-Hu, Yu Bin, Wei Bo, Yang Yuan-Jian
Department of Psychiatry and Medical Experimental Center, Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang University, Nanchang 330029, PR China.
Department of Pharmacology, Key Laboratory of Anti-inflammatory and Immunopharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, PR China.
Pharmacol Biochem Behav. 2017 Apr;155:16-23. doi: 10.1016/j.pbb.2017.03.002. Epub 2017 Mar 8.
Hydrogen sulfide (HS) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that HS regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous HS is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant HS-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of HS 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 HS 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 HS donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived HS is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous HS might involve the regulation of NMDAR function.
硫化氢（HS）是一种内源性气体分子，在大脑中作为神经调节剂发挥作用。我们之前报道过，HS调节大鼠杏仁核的突触可塑性并提示恐惧记忆。然而，内源性HS是否是杏仁核长时程增强（LTP）诱导和提示恐惧记忆形成所必需的仍不清楚。在此，我们表明胱硫醚-β-合酶（CBS）是大脑中主要的HS产生酶，在大鼠杏仁核中高度表达。用抑制剂抑制CBS活性可阻止外侧杏仁核（LA）区域中由活动触发的HS生成。用CBS抑制剂孵育脑片可显著阻止丘脑-LA通路中NMDA受体（NMDARs）依赖性LTP的诱导，并且向LA内注射CBS抑制剂会损害大鼠的提示恐惧记忆。值得注意的是，用HS供体而非CBS激活剂处理可显著逆转由CBS抑制引起的LTP和恐惧记忆损伤。从机制上讲，抑制CBS活性导致丘脑-LA通路中NMDAR介导的突触反应减少，而用HS供体处理可恢复NMDAR的功能。总体而言，这些结果表明CBS衍生的HS是大鼠杏仁核突触可塑性和提示恐惧记忆所必需的，内源性HS的作用可能涉及对NMDAR功能的调节。
