Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress

Yuxiang Liang ¹Ying Wang ²Xiao Zhang ³Shanshan Jin ²Yuqian Guo ²Zhaowei Yu ³Xinrui Xu ²Qizhi Shuai ²Zihan Feng ²Binghong Chen ²Ting Liang ²Ruifang Ao ²Jianting Li ²Juan Zhang ²Rui Cao ²Hong Zhao ²Zhaoyang Chen ⁴Zhizhen Liu ²Jun Xie²

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作者信息

1. Department of Biochemistry and Molecular Biology,Shanxi Key Laboratory of Birth Defect and Cell Regeneration,MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China;Experimental Animal Center of Shanxi Medical University,Shanxi Key Laboratory of Human Disease and Animal Models,Taiyuan 030001,China
2. Department of Biochemistry and Molecular Biology,Shanxi Key Laboratory of Birth Defect and Cell Regeneration,MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China
3. Department of Biochemistry and Molecular Biology,Shanxi Key Laboratory of Birth Defect and Cell Regeneration,MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China;School of Pharmacy,Shanxi Medical University,Taiyuan 030001,China
4. Experimental Animal Center of Shanxi Medical University,Shanxi Key Laboratory of Human Disease and Animal Models,Taiyuan 030001,China
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Abstract

Neural tube defects(NTDs)represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens.Valproic acid(VPA),a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions,has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy.Consequently,urgent efforts are required to identify innovative pre-vention and treatment approaches for VPA-induced NTDs.Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA.Encouragingly,our current data reveal that melatonin(MT)significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA.Moreover,further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure,primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels.In addition,the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs,with significant inhibition ob-served in the affected samples.Notably,MT treatment successfully reinstates Src/PI3K/ERK signaling,thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs.In summary,our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs,thereby offering valuable strategies for the clinical management of VPA-related birth defects.

Key words

melatonin/valproic acid/neural tube defects/reactive oxygen species

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基金项目

国家重点研发计划(2021YFC2301603)

山西省自然科学基金(20210302124041)

山西省自然科学基金(20210302123347)

山西省自然科学基金(20210302124616)

Science and Technology Innovation Plan of Colleges and Universities of Education Department of Shanxi Province(2020L0182)

Open Fund from Key Laboratory of Cellular Physiology(Shanxi Medical University)()

教育部项目(CELLPHYSIOL/SXMU-2021-CPOF202108)

Central Guidance on Local Science and Technology Development Fund for Shanxi Province(YDZJSX2021B008)

Fund for Shanxi Key Subjects Construction(FSKSC)()

国家自然科学基金(82203221)

出版年

2024

生物化学与生物物理学报(英文版)

中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCDCSCD

影响因子：0.772

ISSN：1672-9145

参考文献量59

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