Effects of melatonin on dopaminergic neuron development via IP3-mediated mitochondrial Ca2+ regulation in autism spectrum disorder

被引：2

作者：

Dong, Shuangshan ^{[1
]}

Kifune, Takashi ^{[1
]}

Kato, Hiroki ^{[2
]}

Wang, Lu ^{[1
]}

Kong, Jun ^{[1
]}

Hirofuji, Yuta ^{[1
]}

Sun, Xiao ^{[1
,5
,6
]}

Sato, Hiroshi ^{[1
]}

Ito, Yosuke ^{[1
]}

Kato, Takahiro A. ^{[3
]}

Sakai, Yasunari ^{[4
]}

Ohga, Shouichi ^{[4
]}

Fukumoto, Satoshi ^{[1
]}

Masuda, Keiji ^{[1
]}

机构：

[1] Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Sect Oral Med Children, Maidashi 3-1-1,Higashi Ku, Fukuoka 8128582, Japan

[2] Kyushu Univ, Dept Mol Cell Biol & Oral Anat, Grad Sch Dent Sci, Maidashi 3-1-1,Higashi Ku, Fukuoka 8128582, Japan

[3] Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Maidashi 3-1-1,Higashi Ku, Fukuoka 8128582, Japan

[4] Kyushu Univ Hosp, Grad Sch Med Sci, Dept Pediat, 3-1-1, Maidashi,Higashi ku, Fukuoka 8128582, Japan

[5] Xi An Jiao Tong Univ, Key Lab Shaanxi Prov Craniofacial Precis Med Res, 98 Xiwu Rd, Xian 710004, Peoples R China

[6] Xi An Jiao Tong Univ, Coll Stomatol, Dept Pediat Dent, 98 Xiwu Rd, Xian 710004, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2023年 / 681卷

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

Melatonin; Autism spectrum disorder; Mitochondria; Calcium; Neurodevelopment; PULP STEM-CELLS; DECIDUOUS TEETH; RECEPTORS; CALCIUM; DYSFUNCTION; MT1;

D O I：

10.1016/j.bbrc.2023.09.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：7 / 12

页数：6

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