Zhou Ping, Xu Huai-Sha, Li Meng-Meng, Chen Xiao-Dong, Wang Jun, Zhou Hua-Bin, Chen Ling, Zhang Ning, Liu Na
Department of Medical Psychology, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, 210029, China.
Medical School, Nanjing University, Nanjing, 210093, China.
Behav Brain Res. 2018 Nov 1;353:32-39. doi: 10.1016/j.bbr.2018.06.028. Epub 2018 Jun 25.
Predators induce defensive responses and fear behaviours in prey. The rat exposure test (RET) is frequently used as an animal model of panic. Nitric oxide (NO) which has been reported to be activated by the NMDA receptor, in turn mediates calcium/calmodulin-dependent protein kinase II (CaMKII) signalling pathways in defensive responses. ACCN2, the orthologous human gene of acid-sensing ion channel 1a (ASIC1a), is also associated with panic disorder; however, few studies have focused on the role of ASIC1a in the modulation of panic and calcium/CaMKII signalling by NO. In the present study, NG-nitro-L-arginine-methyl-ester (L-NAME; non-selective NOS inhibitor), S-nitroso-N-acetyl-D,L-penicillamine (SNAP; NO donor), and psalmotoxin (PcTx-1; selective ASIC1a blocker) were administered to the dorsal periaqueductal grey (dPAG) before the predator stimulus, and the roles of NO in the expression of ASIC1a, phosphorylation of CaMKIIα (p-CaMKIIα) and expression of calmodulin (CaM) were investigated. The effects of ASIC1a, p-CaMKIIα and CaM regulation were also examined. Our results showed that intra-dPAG infusion of L-NAME weakened panic-like behaviour and decreased ASIC1a, p-CaMKIIα and CaM expression levels, whereas intra-dPAG infusion of SNAP enhanced panic-like behaviour and increased ASIC1a, p-CaMKIIα and CaM levels. Intra-dPAG infusion of PcTx-1 also weakened panic-like behaviour and decreased p-CaMKIIα expression level. Taken together, these results indicate that NO and ASIC1a are involved in the modulation of RET-induced panic-like behaviour in the dPAG. NO regulates the calcium/CaMKII signalling pathways, and ASIC1a participates in this regulation.
捕食者会引发猎物的防御反应和恐惧行为。大鼠暴露试验（RET）常被用作恐慌的动物模型。据报道，一氧化氮（NO）由N-甲基-D-天冬氨酸受体激活，进而在防御反应中介导钙/钙调蛋白依赖性蛋白激酶II（CaMKII）信号通路。酸敏感离子通道1a（ASIC1a）的直系同源人类基因ACCN2也与恐慌症有关；然而，很少有研究关注ASIC1a在NO对恐慌和钙/CaMKII信号的调节中的作用。在本研究中，在捕食者刺激前，将N-硝基-L-精氨酸甲酯（L-NAME；非选择性一氧化氮合酶抑制剂）、S-亚硝基-N-乙酰-D,L-青霉胺（SNAP；NO供体）和Psalmotoxin（PcTx-1；选择性ASIC1a阻滞剂）注入中脑导水管周围灰质背侧（dPAG），并研究NO在ASIC1a表达、CaMKIIα磷酸化（p-CaMKIIα）和钙调蛋白（CaM）表达中的作用。还检测了ASIC1a、p-CaMKIIα和CaM调节的影响。我们的结果表明，向dPAG内注入L-NAME会减弱恐慌样行为，并降低ASIC1a、p-CaMKIIα和CaM的表达水平，而向dPAG内注入SNAP会增强恐慌样行为，并提高ASIC1a、p-CaMKIIα和CaM的水平。向dPAG内注入PcTx-1也会减弱恐慌样行为，并降低p-CaMKIIα的表达水平。综上所述，这些结果表明NO和ASIC1a参与了dPAG中RET诱导的恐慌样行为的调节。NO调节钙/CaMKII信号通路，ASIC1a参与这一调节过程。
