Neuropeptide S precursor knockout mice display memory and arousal deficits

Autor:	Hans-Christian Pape, Rainer K. Reinscheid, Celia Garau, Kay Jüngling, Wei Si, Stefan Schulz, Xiaobin Liu
Rok vydání:	2017
Předmět:	inorganic chemicals 0301 basic medicine Genetically modified mouse Male medicine.medical_specialty Heterozygote Memory Long-Term education Inhibitory postsynaptic potential Arousal Cell Line 03 medical and health sciences Mice 0302 clinical medicine Internal medicine Neuropeptide S medicine Animals Receptor health care economics and organizations Hole-board test Chemistry General Neuroscience Homozygote Neuropeptides technology industry and agriculture respiratory system Mice Inbred C57BL 030104 developmental biology Endocrinology Knockout mouse Exploratory Behavior Wakefulness Female Neuroscience 030217 neurology & neurosurgery Stress Psychological
Zdroj:	The European journal of neuroscience. 46(1)
ISSN:	1460-9568
Popis:	Activation of neuropeptide S (NPS) signaling has been found to produce arousal, wakefulness, anxiolytic-like behaviors, and enhanced memory formation. In order to further study physiological functions of the NPS system, we generated NPS precursor knockout mice by homologous recombination in embryonic stem cells. NPS-/- mice were viable, fertile, and anatomically normal, when compared to their wild-type and heterozygous littermates. The total number of NPS neurons-although no longer synthesizing the peptide - was not affected by the knockout, as analyzed in NPS-/- /NPSEGFP double transgenic mice. Analysis of behavioral phenotypes revealed significant deficits in exploratory activity in NPS-/- mice. NPS precursor knockout mice displayed attenuated arousal in the hole board test, visible as reduced total nose pokes and number of holes inspected, that was not confounded by increased repetitive or stereotypic behavior. Importantly, long-term memory was significantly impaired in NPS-/- mice in the inhibitory avoidance paradigm. NPS precursor knockout mice displayed mildly increased anxiety-like behaviors in three different tests measuring responses to stress and novelty. Interestingly, heterozygous littermates often presented behavioral deficits similar to NPS-/- mice or displayed intermediate phenotype. These observations may suggest limited ligand availability in critical neural circuits. Overall, phenotypical changes in NPS-/- mice are similar to those observed in NPS receptor knockout mice and support earlier findings that suggest major functions of the NPS system in arousal, regulation of anxiety and stress, and memory formation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::674f571604395bb693500f3dad3413aa https://pubmed.ncbi.nlm.nih.gov/28548278 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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