Elevated Serum Homocysteine Levels Impair Embryonic Neurodevelopment by Dysregulating the Heat Shock Proteins.

IF 2.7 4区 医学 Q2 DEVELOPMENTAL BIOLOGY
Jia Mai, Ling Yang, Min Wang, Jia-Min Deng, Min Min, Hong-Jian Xie, Yong-Mei Jiang, Hua-Qin Sun, Xiao-Juan Liu
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引用次数: 0

Abstract

Observational studies have found that elevated serum homocysteine (Hcy) levels during pregnancy may be associated with the occurrence of neural tube defects (NTDs). However, the effect of Hcy on fetal neural development and its underlying molecular mechanisms remains unclear. To uncover the molecular mechanism, we analyzed the serum Hcy concentration in pregnant women with normal and abnormal pregnancy outcomes and treated zebrafish model embryos with high Hcy. Our findings indicate that elevated serum Hcy levels during pregnancy are associated with adverse pregnancy outcomes. Using the zebrafish model and transcriptome analysis, we found that high Hcy levels led to developmental neural malformations in embryos and affected the expression of key genes at various stages of neural development. Interestingly, deep transcriptome analysis showed that dysregulated heat shock proteins (HSP) might play a key role in high Hcy-mediated alterations in neural development. Importantly, the inhibition of HSP significantly restored the embryonic neuroteratogenic effects induced by high Hcy levels in the zebrafish model. In summary, our findings provide a novel molecular pathogenic mechanism in which ectopic HSP is associated with neural development defects caused by high Hcy levels, suggesting potential prevention and targeted therapies for high Hcy level-related NTDs during pregnancy.

血清同型半胱氨酸水平升高会通过调节热休克蛋白损害胚胎神经发育
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来源期刊
Developmental Neurobiology
Developmental Neurobiology 生物-发育生物学
CiteScore
6.50
自引率
0.00%
发文量
45
审稿时长
4-8 weeks
期刊介绍: Developmental Neurobiology (previously the Journal of Neurobiology ) publishes original research articles on development, regeneration, repair and plasticity of the nervous system and on the ontogeny of behavior. High quality contributions in these areas are solicited, with an emphasis on experimental as opposed to purely descriptive work. The Journal also will consider manuscripts reporting novel approaches and techniques for the study of the development of the nervous system as well as occasional special issues on topics of significant current interest. We welcome suggestions on possible topics from our readers.
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