期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 681, 期 -, 页码 7-12出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2023.09.050
关键词
Melatonin; Autism spectrum disorder; Mitochondria; Calcium; Neurodevelopment
Melatonin entrains circadian rhythms through MT1 and MT2 receptors, and has neuroprotective and mitochondrial activating effects. This study used deciduous tooth-derived stem cells to model neurodevelopmental defects in autism spectrum disorder (ASD), and found that melatonin supplementation improved dopaminergic system development by modulating mitochondrial Ca2+ homeostasis via MT1/MT2 receptors.
Melatonin entrainment of suprachiasmatic nucleus-regulating circadian rhythms is mediated by MT1 and MT2 receptors. Melatonin also has neuroprotective and mitochondrial activating effects, suggesting it may affect neurodevelopment. We studied melatonin's pharmacological effects on autism spectrum disorder (ASD) neuropathology. Deciduous tooth-derived stem cells from children with ASD were used to model neurodevelopmental defects and differentiated into dopaminergic neurons (ASD-DNs) with or without melatonin. Without melatonin, ASD-DNs had reduced neurite outgrowth, mitochondrial dysfunction, lower mitochondrial Ca2+ levels, and Ca2+ accumulation in the endoplasmic reticulum (ER) compared to control DNs from typically developing childrenderived stem cells. Melatonin enhanced IP3-dependent Ca2+ release from ER to mitochondria, improving mitochondrial function and neurite outgrowth in ASD-DNs. Luzindole, an MT1/MT2 antagonist, blocked these effects. Thus, melatonin supplementation may improve dopaminergic system development in ASD by modulating mitochondrial Ca2+ homeostasis via MT1/MT2 receptors.
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