Medical School, Nanjing University, Nanjing, 210093, China.
Department of Medical Psychology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, 210029, China.
Biochem Biophys Res Commun. 2019 Apr 2;511(2):274-279. doi: 10.1016/j.bbrc.2019.02.020. Epub 2019 Feb 12.
Panic disorder (PD) is a multifactorial neuropsychiatric disorder. Our previous study has demonstrated that the nitric oxide (NO) pathway and the acid-sensing ion channel 1a (ASIC1a) level in the dorsal midbrain periaqueductal gray (dPAG) are involved in the modulation of panic-like responses. In addition, the prefrontal cortex (PFC) and the hippocampus also play a role in panic-like responses. However, no studies have investigated the protein level of ASIC1a in the PFC and hippocampus in a mouse model of panic-like disorders after alteration of the NO pathway in the dPAG. We investigated the production of a panic attack with intra-dPAG injections of SNAP, an NO donor, and 7-NI, an nNOS inhibitor. Moreover, we measured ASIC1a protein levels in the PFC and hippocampus. The rat exposure test (RET) is frequently used as an animal model of panic. In our study, C57BL/6 mice received an intra-dPAG injection of SNAP or 7-NI before RET; neurobehavioral tests were then conducted, followed by mechanistic evaluation through western blot analysis in the PFC and hippocampus. An intra-dPAG infusion of SNAP significantly increased the panic-like effect, whereas treatment with 7-NI decreased fear behavior. Mice treated with SNAP/7-NI showed significantly increased/decreased ASIC1a expression in the PFC, and a decreasing/increasing trend in the hippocampus. The present study suggests that the NO pathway in the dPAG plays a key role in panic-like responses in mice confronted by a rat, further, NO intra-dPAG injection also modulates the ASIC1a expression levels in the PFC and hippocampus.
惊恐障碍（PD）是一种多因素的神经精神疾病。我们之前的研究表明，中脑导水管周围灰质（dPAG）背侧的一氧化氮（NO）通路和酸感应离子通道 1a（ASIC1a）水平参与了惊恐样反应的调节。此外，前额叶皮层（PFC）和海马体在惊恐样反应中也发挥作用。然而，目前还没有研究调查在 dPAG 中的 NO 通路改变后，惊恐样障碍的小鼠模型中 PFC 和海马体中的 ASIC1a 蛋白水平。我们通过在 dPAG 内注射 NO 供体 SNAP 和 nNOS 抑制剂 7-NI 来研究惊恐发作的产生。此外，我们测量了 PFC 和海马体中的 ASIC1a 蛋白水平。大鼠暴露测试（RET）常用于惊恐的动物模型。在我们的研究中，C57BL/6 小鼠在 RET 前接受 dPAG 内注射 SNAP 或 7-NI；然后进行神经行为测试，接着通过 Western blot 分析在 PFC 和海马体中进行机制评估。dPAG 内注射 SNAP 显著增加了惊恐样效应，而 7-NI 处理则降低了恐惧行为。SNAP/7-NI 处理的小鼠在 PFC 中表现出明显增加/减少的 ASIC1a 表达，在海马体中表现出减少/增加的趋势。本研究表明，dPAG 中的 NO 通路在面对大鼠的小鼠的惊恐样反应中起着关键作用，此外，NO 内 dPAG 注射还调节了 PFC 和海马体中的 ASIC1a 表达水平。
