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, Lanzhou, PR China.
Department of Anesthesiology, Lishan Hospital of the Anshan Central Hospital, Anshan, PR China.
Chem Senses. 2020 Apr 17;45(3):195-202. doi: 10.1093/chemse/bjaa003.
Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.
神经肽 S（NPS）是一种内源性肽，最近被认为存在于脑干中，并被认为在维持记忆方面发挥着重要作用。NPS 或 NPS 受体（NPSR）在小鼠中的缺失显示出记忆形成缺陷。我们最近的研究表明，中枢给予 NPS 可促进嗅觉功能，并改善毒蕈碱型胆碱能受体拮抗剂和 N-甲基-D-天冬氨酸受体拮抗剂诱导的嗅觉空间记忆障碍。然而，内源性 NPS 是否是控制嗅觉空间记忆所必需的神经调质仍有待确定。在这项研究中，我们使用计算机辅助的 4 孔板嗅觉空间记忆测试，研究了 NPSR 肽类拮抗剂 [D-Val5]NPS（10 和 20 nmol，侧脑室）和非肽类拮抗剂 SHA 68（10 和 50 mg/kg，腹腔内）对嗅觉空间记忆的影响。此外，免疫荧光用于鉴定 c-Fos 和 NPSR 免疫反应性（-ir）神经元在嗅觉系统和海马结构中的分布，这些区域与嗅觉空间记忆密切相关。[D-Val5]NPS 剂量为 20 nmol 和 SHA 68 剂量为 50 mg/kg 显著减少了在回忆试验中对空间上交换的 2 种气味的访问次数，交换了气味，同时减少了 NPSR-ir 神经元中 Fos-ir 的百分比，这些神经元在嗅球、梨状皮层、下托、前下托和副下托中密集分布。这些发现表明，内源性 NPS 是嗅觉空间记忆的关键神经调质。
