抑制 iNOS 可改善创伤性应激引起的突触可塑性和记忆缺陷。

Inhibition of iNOS ameliorates traumatic stress-induced deficits in synaptic plasticity and memory.

机构信息

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanpingnan Road #600, Shanghai, China.

出版信息

Psychiatry Res. 2018 Oct;268:413-418. doi: 10.1016/j.psychres.2018.08.028. Epub 2018 Aug 13.

DOI:10.1016/j.psychres.2018.08.028

Abstract

Post-traumatic stress disorder (PTSD) is characterized by cognitive deficits including impaired explicit memory. Nitric oxide (NO), which is generated by nitric oxide synthase (NOS), has been considered to modulate learning and memory. In current study, we evaluated the role of NOS in the mouse model of PTSD. We established the immobilization (IMO) mouse model of PTSD and analyzed mice behavior, NOS expression and hippocampal excitatory synaptic transmission after immobilization. We inhibited iNOS by applying of iNOS inhibitor 1400 W and monitored the effect of iNOS inhibition by 1400 W in IMO mice. IMO induced iNOS expression and resulted in abnormal behavior and deficits in synaptic plasticity and memory in mice. Inhibition of iNOS rescued abnormal hippocampal long-term potentiation and abnormal behavior in IMO mice. Inhibition of iNOS ameliorates traumatic stress-induced deficits in synaptic plasticity and memory.

摘要

创伤后应激障碍（PTSD）的特征是认知缺陷，包括明显记忆受损。一氧化氮（NO）由一氧化氮合酶（NOS）产生，被认为可以调节学习和记忆。在本研究中，我们评估了 NOS 在 PTSD 小鼠模型中的作用。我们建立了 PTSD 的束缚（IMO）小鼠模型，并在束缚后分析了小鼠的行为、NOS 表达和海马兴奋性突触传递。我们通过应用 NOS 抑制剂 1400W 抑制 iNOS，并监测 1400W 在 IMO 小鼠中的抑制作用。IMO 诱导 iNOS 表达，导致小鼠异常行为以及突触可塑性和记忆缺陷。NOS 抑制可挽救 IMO 小鼠海马长时程增强和异常行为。NOS 抑制可改善创伤应激引起的突触可塑性和记忆缺陷。