caa a22 4500 606203338 CHVBK 20210128100957.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s00429-014-0716-x doi (NATIONALLICENCE)springer-10.1007/s00429-014-0716-x Early-life sleep deprivation persistently depresses melatonin production and bio-energetics of the pineal gland: potential implications for the development of metabolic deficiency [Elektronische Daten] [Li-You Chen, Cheng Tiong, Chung-Hung Tsai, Wen-Chieh Liao, Shun-Fa Yang, Su-Chung Youn, Fu-Der Mai, Hung-Ming Chang] 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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ signaling along with intense adrenoreceptors, PKA, and pCREB activities were all detected in pinealocytes. Enhanced Ca2+ imaging and signaling pathway corresponded well with intact bio-energetics, normal melatonin production and metabolic activity. However, following ESD, not only Ca2+ but also pineal signaling activities were all significantly decreased. Blood analysis showed reduced melatonin level and impaired metabolic function after ESD. As depressed Ca2+-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. Springer-Verlag Berlin Heidelberg, 2014 Childhood sleep deprivation nationallicence Metabolic deficiency nationallicence Melatonin nationallicence Pineal function nationallicence Calcium nationallicence Ionic imaging analysis nationallicence Chen Li-You Institute of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut Tiong Cheng Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, 110, Taipei, Taiwan aut Tsai Chung-Hung Institute of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut Liao Wen-Chieh Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut Yang Shun-Fa Institute of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut Youn Su-Chung Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut Mai Fu-Der Department of Biochemistry, School of Medicine, College of Medicine, Taipei Medical University, 110, Taipei, Taiwan aut Chang Hung-Ming Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, 250, Wu-Hsing Street, 110, Taipei, Taiwan aut Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 663-676 1863-2653 220:2<663 2015 220 429 https://doi.org/10.1007/s00429-014-0716-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0716-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chen Li-You Institute of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Tiong Cheng Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, 110, Taipei, Taiwan aut NATIONALLICENCE 700 1- Tsai Chung-Hung Institute of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Liao Wen-Chieh Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Yang Shun-Fa Institute of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Youn Su-Chung Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Mai Fu-Der Department of Biochemistry, School of Medicine, College of Medicine, Taipei Medical University, 110, Taipei, Taiwan aut NATIONALLICENCE 700 1- Chang Hung-Ming Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, 250, Wu-Hsing Street, 110, Taipei, Taiwan aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 663-676 1863-2653 220:2<663 2015 220 429