8-Nitro-cGMP attenuates context-dependent fear memory in mice.
8-Nitro-cGMP attenuates context-dependent fear memory in mice.
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8-Nitro-cGMP 减弱小鼠情境依赖性恐惧记忆。
DOI：
10.1016/j.bbrc.2019.01.138
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Ihara H.
中科院分区：
文献类型：
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作者：
Kishimoto Y;Kasamatsu S;Yanai S;Endo S;Akaike T;Ihara H.
我们之前报道过8-硝基鸟苷3 ',5 ' -环单磷酸（8-硝基cGMP）是通过一氧化氮/活性氧信号通路内源性产生的，它通过s -鸟苷化与蛋白质巯基残基反应，将cGMP结构添加到蛋白质上。s -鸟苷化发生在突触体相关蛋白25 （SNAP-25）上，SNAP-25是调节胞外分泌的可溶性乙基丙烯酰亚胺敏感因子附着蛋白受体（SNARE）复合物的一部分。然而，8-硝基- cgmp在神经系统中的生物学意义尚不清楚。在此，我们研究了脑室内（icv）输注8-硝基- cgmp对小鼠脑功能的影响。开放性实验和恐惧调节任务的结果显示，icv输注8-硝基- cgmp降低了小鼠的垂直活动和情境依赖性恐惧记忆，这两者都与海马有关。免疫组化分析显示8-硝基cgmp灌注小鼠齿状回c- fos阳性细胞增加。此外，生化分析表明，icv输注8-硝基- cgmp增加了s -鸟苷化蛋白，包括SNAP-25和SNARE复合物的形成，并减少了含有复杂蛋白的复合物，复杂蛋白通过与SNARE复合物结合来调节海马胞吐。这些发现表明，8-硝基cgmp在海马中的积累会通过海马蛋白（如SNAP-25）的胍基化影响其功能，包括记忆。
We previously reported that 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) is endogenously produced via nitric oxide/reactive oxygen species signaling pathways and it reacts with protein thiol residues to add cGMP structure to proteins throughS-guanylation.S-Guanylation occurs on synaptosomal-associated protein 25 (SNAP-25), which is a part of the solubleN-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that regulates exocytosis. However, the biological relevance of 8-nitro-cGMP in the nervous system remains unclear. Here, we investigated the effects of intracerebroventricular (icv) infusion of 8-nitro-cGMP on mouse brain functions. The results of an open-field test and fear-conditioning task revealed that icv infusion of 8-nitro-cGMP decreased the vertical activity and context-dependent fear memory of mice, which are both associated with the hippocampus. Immunohistochemical analysis revealed increased c-Fos-positive cells in the dentate gyrus in 8-nitro-cGMP-infused mice. Further, biochemical analyses showed that icv infusion of 8-nitro-cGMP increasedS-guanylated proteins including SNAP-25 and SNARE complex formation as well as decreased complexes containing complexin, which regulates exocytosis by binding to the SNARE complex, in the hippocampus. These findings suggest that accumulation of 8-nitro-cGMP in the hippocampus affects its functions, including memory, viaS-guanylation of hippocampal proteins such as SNAP-25.