2018年1月10日
Restoring serotonergic homeostasis in the lateral hypothalamus rescues sleep disturbances induced by early-life obesity
Journal of Neuroscience
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- 巻
- 38
- 号
- 2
- 開始ページ
- 441
- 終了ページ
- 451
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1523/JNEUROSCI.1333-17.2017
© 2018 the authors. Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep–wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep–wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep–wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3–36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep–wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep.
- リンク情報
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- DOI
- https://doi.org/10.1523/JNEUROSCI.1333-17.2017
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/29196316
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596113
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85040525959&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85040525959&origin=inward
- ID情報
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- DOI : 10.1523/JNEUROSCI.1333-17.2017
- ISSN : 0270-6474
- eISSN : 1529-2401
- PubMed ID : 29196316
- PubMed Central 記事ID : PMC6596113
- SCOPUS ID : 85040525959