The gut–brain peptide neuromedin U is involved in the mammalian circadian oscillator system
Abstract
Immunohistochemical analysis revealed the presence of a gut-brain peptide, neuromedin U (NMU), in the suprachiasmatic nucleus (SCN), which is the site of the master circadian oscillator. The expression of NMU mRNA exhibited a circadian rhythm, with the peak expression in the SCN occurring at CT4-8h. The two NMU-binding receptors (NMU-R1 and NMU-R2) were also expressed in the SCN, but their phase angles were different. Intracerebroventricular injection (ICV) of NMU induced the expression of Fos protein in the SCN cells and caused a phase-dependent phase shift of the circadian locomotor activity rhythm. The magnitude of the phase shift was dose dependent. This NMU-induced phase shift was of the nonphotic type. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed increases in the expression in the SCN of immediate early genes, such as c-fos, NGFI-A, NGFI-B, and JunB. Furthermore, ICV injection of NMU increased the expression of Per1, but not Per2, in the SCN. These results indicate that NMU may play some important role in the circadian oscillator by exerting an autocrine or paracrine action in the SCN.
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eQTL, PheWAS, and model organism evidence support the hypothesis that introgressed alleles downregulate NMUR2 in the brain leading to increased morningness.
“In the Supplemental Text, we describe eQTL, PheWAS, and model organism evidence supporting the hypothesis that introgressed alleles downregulate NMUR2 in the brain leading to increased morningness61–65.”
From Quantifying the contribution of Neanderthal introgression to the heritability of complex traits (2021) · cites this paper as [62]
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Patterns of Positive Selection in Six Mammalian Genomes
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- Authors
- Nakahara, K., Hanada, R., Murakami, N., Teranishi, H., Ohgusu, H., Fukushima, N., Moriyama, M., Ida, T., Kangawa, K., & Kojima, M.
- Affiliations
- University of Miyazaki (JP)
- Kurume University (JP)
- National Cerebral and Cardiovascular Center (JP)
- Corresponding author
- Murakami, Noboru
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 318
- Issue
- 1
- Pages
- 156-161
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2162900707
- Cited by
- 76
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 4 · 2017: 8 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Naito Foundation
- Mitsubishi Foundation
- Takeda Science Foundation
- Brain Science Foundation
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- neuromedin U, circadian rhythm, suprachiasmatic nucleus, circadian clock, phase shift, non-photic entrainment, Fos expression, immediate early genes, Per1, autocrine and paracrine signaling, brain-gut peptides
- MeSH terms
- Animals, Circadian Rhythm, Immunohistochemistry, Injections, Intraventricular, Male, Membrane Proteins, Neurons, Neuropeptides, Nuclear Proteins, RNA, Messenger, Suprachiasmatic Nucleus, Transcription Factors, Gene Expression, Genes, jun, Genes, fos, Rats, Wistar, Immediate-Early Proteins, Receptors, Neurotransmitter, Cell Cycle Proteins, Rats, Period Circadian Proteins
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