Hydrogen Sulfide Reverses Aging-Associated Amygdalar Synaptic Plasticity and Fear Memory Deficits in Rats.
Hydrogen Sulfide Reverses Aging-Associated Amygdalar Synaptic Plasticity and Fear Memory Deficits in Rats.
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硫化氢可逆转大鼠与衰老相关的杏仁核突触可塑性和恐惧记忆缺陷
DOI：
10.3389/fnins.2018.00390
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发表时间：
2018
影响因子：
4.3
通讯作者：
Yang YJ
中科院分区：
文献类型：
--
作者：
Zhan JQ;Zheng LL;Chen HB;Yu B;Wang W;Wang T;Ruan B;Pan BX;Chen JR;Li XF;Wei B;Yang YJ
作为一种内源性神经调节剂，硫化氢 (H2S) 在大脑中发挥多种生物效应。先前的研究表明，H2S 参与健康啮齿动物神经突触可塑性和认知的调节。众所周知，随着年龄的增长，认知功能会逐渐下降。本研究的目的是调查 H2S 在与衰老相关的杏仁核突触可塑性和提示恐惧记忆缺陷中的作用，并探讨其潜在机制。我们发现，与健康成年大鼠相比，老年大鼠杏仁核中的 H2S 水平显着降低，这表明丘脑外侧杏仁核 (LA) 通路的长时程增强 (LTP) 和杏仁核依赖性提示恐惧记忆存在显着缺陷。使用 H2S 供体硫化氢 (NaHS) 进行沐浴可显着逆转老年大鼠脑切片中受损的 LTP，而 LA 内输注 NaHS 则可恢复老年大鼠的暗示恐惧记忆。从机制上讲，我们发现 H2S 治疗显着增强了老年大鼠丘脑-LA 通路中 NMDAR 介导的突触反应。值得注意的是，含 GluN2B 的 NMDAR，而不是含 GluN2A 的 NMDAR，导致了 H2S 对衰老相关的杏仁核 LTP 和恐惧记忆损伤的影响，因为应用 GluN2B 拮抗剂可能消除 NaHS 治疗对老年大鼠杏仁核 LTP 和认知能力的有益影响。总的来说，这些结果表明，H2S 可以通过恢复含有 GluN2B 的 NMDAR 的功能来逆转与衰老相关的杏仁核突触可塑性和恐惧记忆缺陷，这表明补充 H2S 可能是与衰老相关的认知障碍的一种治疗方法。
As an endogenous neuromodulator, hydrogen sulfide (H2S) exerts multiple biological effects in the brain. Previous studies have shown that H2S is involved in the regulation of neural synaptic plasticity and cognition in healthy rodents. It is well known that there is a progressive decline of cognitive function that occurs with increased age. The purpose of this study was to investigate the role of H2S in aging-associated amygdalar synaptic plasticity and cued fear memory deficits as well as to explore the underlying mechanisms. We found that H2S levels in the amygdala were significantly lower in aged rats when compared with healthy adult rates, which displayed significant deficits in long-term potentiation (LTP) in the thalamo-lateral amygdala (LA) pathway and amygdala-dependent cued fear memory. Bath application of an H2S donor, sodium hydrogen sulfide (NaHS), significantly reversed the impaired LTP in brain slices from aged rats, and intra-LA infusion of NaHS restored the cued fear memory in aged rats. Mechanismly, we found that H2S treatment significantly enhanced NMDAR-mediated synaptic responses in the thalamo-LA pathway of aged rats. Notably, GluN2B-containing NMDARs, but not GluN2A-containing NMDARs, contributed to the effects of H2S on aging-associated impairments of amygdalar LTP and fear memory, because applying GluN2B antagonist could abolish the beneficial effects of NaHS treatment on amygdalar LTP and cognitive performance in aged rats. Collectively, these results show that H2S can reverse aging-associated amygdalar synaptic plasticity and fear memory deficits by restoring the function of GluN2B-containing NMDARs, suggesting that supplement of H2S might be a therapeutic approach for aging-related cognitive disorders.
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影响因子：
64.8
作者：
通讯作者：
--
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。
影响因子：
3.6
作者：
Chen, Hai-Bo;Wu, Wen-Ning;Yang, Yuan-Jian
通讯作者：
Yang, Yuan-Jian
影响因子：
2.7
作者：
Giuliani, Daniela;Ottani, Alessandra;Guarini, Salvatore
通讯作者：
Guarini, Salvatore
影响因子：
2.7
作者：
Das, Siba R.;Magnusson, Kathy R.
通讯作者：
Magnusson, Kathy R.
影响因子：
2.3
作者：
Liu, Ping;Smith, Paul F.;Darlington, Cynthia L.
通讯作者：
Darlington, Cynthia L.