TY - JOUR
T1 - Effects of melatonin on dopaminergic neuron development via IP3-mediated mitochondrial Ca2+ regulation in autism spectrum disorder
AU - Dong, Shuangshan
AU - Kifune, Takashi
AU - Kato, Hiroki
AU - Wang, Lu
AU - Kong, Jun
AU - Hirofuji, Yuta
AU - Sun, Xiao
AU - Sato, Hiroshi
AU - Ito, Yosuke
AU - Kato, Takahiro A.
AU - Sakai, Yasunari
AU - Ohga, Shouichi
AU - Fukumoto, Satoshi
AU - Masuda, Keiji
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/11/12
Y1 - 2023/11/12
N2 - 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 children-derived 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.
AB - 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 children-derived 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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U2 - 10.1016/j.bbrc.2023.09.050
DO - 10.1016/j.bbrc.2023.09.050
M3 - Article
C2 - 37742475
AN - SCOPUS:85171597934
SN - 0006-291X
VL - 681
SP - 7
EP - 12
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -