Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.
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.
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.
Yu-Feng
YF
Shao
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.
Can
C
Wang
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.
Jun-Fan
JF
Xie
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.
Xiang-Pan
XP
Kong
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.
Le
L
Xin
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.
Chao-Yu
CY
Dong
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.
Jing
J
Li
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.
Wen-Ting
WT
Ren
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. houyiping@lzu.edu.cn.
Yi-Ping
YP
Hou
D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000008:administration & dosage / Q000502:physiology*; D009812:Odorants; D055696:Olfactory Perception / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism / Q000502:physiology*; D012601:Scopolamine / Q000008:administration & dosage; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology*
D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D018013:Receptors, Neuropeptide; C583532:neuropeptide S receptor, mouse; C539972:neuropeptide S, mouse; D016291:Dizocilpine Maleate; D012601:Scopolamine
Antagonist; Muscarinic cholinergic receptor; N-methyl-D-aspartate receptor; Neuropeptide S (NPS); Neuropeptide S receptor (NPSR); Olfactory spatial memory; Subiculum complex; c-Fos