Jing Zhi-Hua, Wei Xiao-Ming, Wang Shao-Hu, Chen Yu-Fen, Liu Li-Xia, Qi Wen-Xiu
Basic Medical College, Shanxi Medical University, Taiyuan 030001, China; Department of Physiology, Nanyang Medical College, Nanyang 473061, China; Department of Physiology, Fenyang College of Shanxi Medical University, Fenyang 032200, China.
Sheng Li Xue Bao. 2014 Jun 25;66(3):307-14.
The aim of the present study is to explore the interaction of nitric oxide (NO) and nicotinic acetylcholine receptor (nAChR) on learning and memory of rats. Rats were intracerebroventricularly (i.c.v.) injected with L-arginine (L-Arg, the NO precursor) (L-Arg group) or choline chloride (CC, an agonist of α7nAChR) (CC group), and with combined injection of L-Arg and CC (L-Arg+CC group), and methyllycaconitine (MLA, α7nAChR antagonist) or N(ω)-nitro-L-arginine methylester (L-NAME, nitric oxide synthase inhibitor) i.c.v. injected first and followed by administration of L-Arg combined with CC (MLA+L-Arg+CC group or L-NAME+L-Arg+CC group), respectively, and normal saline was used as control (NS group). The learning and memory ability of rats was tested with Y-maze; the level of NO and the expressions of neuronal nitric oxide synthase (nNOS) or α7nAChR in hippocampus were measured by NO assay kit, immunohistochemistry or Western blot. The results showed that compared with L-Arg group or CC group, the rats' learning and memory behavioral ability in Y-maze was observably enhanced and the level of NO, the optical density of nNOS-like immunoreactivity (LI) or α7nAChR-LI in hippocampus were significantly increased in L-Arg+CC group; Compared with L-Arg+CC group, the ability of learning and memory and the level of NO as well as the expressions of nNOS-LI or α7nAChR-LI were obviously decreased in MLA+L-Arg+CC group or in L-NAME+L-Arg+CC group. In conclusion, i.c.v. administration of L-Arg combined with CC significantly improved the action of the L-Arg or CC on the content of NO and the nNOS or α7nAChR expressions in hippocampus along with the learning and memory behavior of rats; when nNOS or α7nAChR was interrupted in advance, the effects of L-Arg combined with CC were also suppressed. The results suggest that there are probably synergistic effects between NO and nAChR on learning and memory.
本研究旨在探讨一氧化氮(NO)与烟碱型乙酰胆碱受体(nAChR)对大鼠学习记忆的相互作用。将大鼠脑室内(i.c.v.)注射L-精氨酸(L-Arg,NO前体)(L-Arg组)或氯化胆碱(CC,α7nAChR激动剂)(CC组),以及联合注射L-Arg和CC(L-Arg+CC组),并先脑室内注射甲基lycaconitine(MLA,α7nAChR拮抗剂)或N(ω)-硝基-L-精氨酸甲酯(L-NAME,一氧化氮合酶抑制剂),随后分别给予L-Arg与CC联合用药(MLA+L-Arg+CC组或L-NAME+L-Arg+CC组),以生理盐水作为对照(NS组)。用Y迷宫测试大鼠的学习记忆能力;用NO检测试剂盒、免疫组织化学或蛋白质免疫印迹法检测海马中NO水平以及神经元型一氧化氮合酶(nNOS)或α7nAChR的表达。结果显示,与L-Arg组或CC组相比,L-Arg+CC组大鼠在Y迷宫中的学习记忆行为能力明显增强,海马中NO水平、nNOS样免疫反应性(LI)或α7nAChR-LI的光密度显著增加;与L-Arg+CC组相比,MLA+L-Arg+CC组或L-NAME+L-Arg+CC组的学习记忆能力、NO水平以及nNOS-LI或α7nAChR-LI的表达明显降低。总之,脑室内给予L-Arg与CC联合用药显著改善了L-Arg或CC对海马中NO含量、nNOS或α7nAChR表达以及大鼠学习记忆行为的作用;当nNOS或α7nAChR预先被阻断时,L-Arg与CC联合用药的效果也受到抑制。结果表明,NO与nAChR在学习记忆方面可能存在协同作用。