Early-life sleep deprivation persistently depresses melatonin production and bio-energetics of the pineal gland: potential implications for the development of metabolic deficiency

Li You Chen, C. Tiong, Chung Hung Tsai, Wen Chieh Liao, Shun Fa Yang, Su Chung Youn, Fu-Der Mai, Hung-Ming Chang

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

Early-life sleep deprivation (ESD) is a serious condition with severe metabolic sequelae. The pineal hormone melatonin plays an important role in homeostatic regulation of metabolic function. Considering norepinephrine-mediated Ca(2+) influx and subsequent protein kinase A (PKA) activation is responsible for downstream cAMP-response element-binding protein (CREB) phosphorylation and melatonin biosynthesis, the present study determined whether Ca(2+) expression, together with the molecular machinery participated in melatonin production would significantly alter after ESD. Weaning rats subjected to chronic ESD and maintained naturally (light:dark cycle = 12:12) to adulthood were processed for time-of-flight secondary ion mass spectrometry, immunoblotting, immunohistochemistry together with spectrometric assay to detect the Ca(2+) signaling, adrenoreceptors, PKA, phosphorylated CREB (pCREB) as well as the serum level of melatonin, respectively. Pineal bio-energetics and metabolic function were determined by measuring the cytochrome oxidase activity and serum level of glucose, triglyceride, insulin, high- and low-density lipoproteins, respectively. Results indicated that in normal rats, strong Ca(2+) signaling along with intense adrenoreceptors, PKA, and pCREB activities were all detected in pinealocytes. Enhanced Ca(2+) imaging and signaling pathway corresponded well with intact bio-energetics, normal melatonin production and metabolic activity. However, following ESD, not only Ca(2+) but also pineal signaling activities were all significantly decreased. Blood analysis showed reduced melatonin level and impaired metabolic function after ESD. As depressed Ca(2+)-mediated signaling pathway and melatonin biosynthesis are positively correlated with the development of metabolic dysfunction, supplementary use of melatonin in childhood may thus serve as a practical way to prevent or counteract the ESD-induced metabolic deficiency.
原文英語
頁(從 - 到)663-676
頁數14
期刊Brain Structure and Function
220
發行號2
DOIs
出版狀態已發佈 - 三月 1 2015
對外發佈Yes

ASJC Scopus subject areas

  • Medicine(all)

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