title: Early-life sleep deprivation persistently depresses melatonin production and bio-energetics of the pineal gland: potential implications for the development of metabolic deficiency.
abstract: 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.
authors: Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan.
authors: Li-You
authors: LY
authors: Chen
authors: Cheng
authors: C
authors: Tiong
authors: Chung-Hung
authors: CH
authors: Tsai
authors: Wen-Chieh
authors: WC
authors: Liao
authors: Shun-Fa
authors: SF
authors: Yang
authors: Su-Chung
authors: SC
authors: Youn
authors: Fu-Der
authors: FD
authors: Mai
authors: Hung-Ming
authors: HM
authors: Chang
mesh_terms: D000367:Age Factors; D000818:Animals; D020013:Calcium Signaling; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000097:blood / Q000378:metabolism*; D008659:Metabolic Diseases / Q000209:etiology*; D010766:Phosphorylation; D010870:Pineal Gland / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism; D015398:Signal Transduction; D012892:Sleep Deprivation / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D011941:Receptors, Adrenergic; D008550:Melatonin