Shao Yu-Feng, Wang Can, Xie Jun-Fan, Kong Xiang-Pan, Xin Le, Dong Chao-Yu, Li Jing, Ren Wen-Ting, Hou Yi-Ping
Departments of Neuroscience, Anatomy, Histology, and Embryology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
Department of Human Anatomy, School of Medicine, Hunan Normal University, 371 Tongzipo Road, Changsha, 410013, People's Republic of China.
Brain Struct Funct. 2016 Jul;221(6):3327-36. doi: 10.1007/s00429-015-1103-y. Epub 2015 Sep 1.
Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice.
我们之前的研究表明，神经肽S（NPS）通过选择性激活嗅觉皮层中表达NPS受体（NPSR）的神经元，促进嗅觉功能。海马结构下托复合体中NPSR mRNA的高水平表达表明，NPS-NPSR系统可能参与嗅觉空间记忆的调节。本研究采用计算机辅助四孔板空间记忆测试，并通过监测小鼠下托复合体中的Fos表达，来研究NPS对东莨菪碱或MK801诱导的嗅觉空间记忆损伤的影响。此外，采用双免疫荧光显微镜鉴定同时表达NPSR的NPS诱导的Fos免疫反应性（-ir）神经元。在训练试验后，向患有东莨菪碱（一种选择性毒蕈碱胆碱能受体拮抗剂）或MK801（一种N-甲基-D-天冬氨酸受体拮抗剂）诱导的嗅觉辨别能力丧失的小鼠脑室内注射NPS（0.5 nmol），显著增加了回忆试验中对转换气味剂的访问次数。NPSR拮抗剂[D-Val(5)]NPS（40 nmol）消除了NPS对嗅觉空间记忆的改善作用。离体c-Fos和NPSR免疫组织化学显示，与溶剂处理的小鼠相比，NPS显著增强了包括下托（S）、前下托（PrS）和旁下托（PaS）的下托复合体中的Fos表达。在S、PrS和PaS中，同时表达NPSR的Fos-ir神经元的百分比分别为91.3%、86.5%和90.0%。本研究结果表明，NPS通过选择性激活下托复合体中表达NPSR的神经元，改善了东莨菪碱和MK801诱导的小鼠嗅觉空间记忆损伤。
