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

• DOI: 10.1007/s00429-014-0716-x
• Publication Date: 2014-02-10T09:51:26Z
• Authors: Li-You Chen; Cheng Tiong; Chung-Hung Tsai; Wen-Chieh Liao; Shun-Fa Yang; Su-Chung Youn; Fu-Der Mai; Hung-Ming Chang
• Keywords: Male; 0301 basic medicine; Age Factors; Pineal Gland; Rats; Receptors, Adrenergic; 03 medical and health sciences; Metabolic Diseases; Animals; Sleep Deprivation; Calcium Signaling; Phosphorylation; Rats, Wistar; Cyclic AMP Response Element-Binding Protein; Melatonin; Signal Transduction

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.