{"title":"Protective Effect of myo-Inositol Against Decitabine-Induced Neural Tube Defects in Embryonic Zebrafish.","authors":"Venugopalan Rajesh, Subramani Karthi, Manni Venkatachari Kumudhavalli","doi":"10.1007/s12640-025-00735-5","DOIUrl":null,"url":null,"abstract":"<p><p>Neural tube defects (NTDs) are severe congenital anomalies affecting 1-2 infants per 1000 births, and are influenced by genetic and environmental factors, with DNA hypomethylation and methylation cycle suppression being key causes. In our earlier investigation, decitabine (DCT) caused multiple NTDs in embryonic zebrafish, supporting this hypothesis. Recent research has emphasized the importance of myo-inositol (MI) in embryonic development and its efficacy in reducing the risk of neural tube defects, even in cases resistant to folate. We aimed to examine the effect of MI on DCT-induced NTDs in an embryonic zebrafish model. The embryos were exposed to 1 mM DCT alone, 50 µM MI with 1 mM DCT, 100 µM MI with 1 mM DCT, and a control group for comparison. The development, hatching, mortality rates, neural tube malformations, and neural tube patterning of developing embryos were monitored and recorded. Exposure to MI significantly reduced the incidence of NTDs in developing embryos. At concentrations of 50 µM and 100 µM, MI provided 35% and 30% protection against DCT-induced neural tube malformation, respectively. Multiple NTDs were significantly reduced in the MI groups, with 1 mM DCT causing 95% defects, 50 µM MI with 1 mM DCT causing 50%, and 100 µM MI with 1 mM DCT causing 55% defects. The DCT-induced hatching delay was also reversed by MI treatment. Alizarin red staining and histopathological observations supported these observations. In the context of neural tube development, the protective effects of MI against DCT-induced NTDs could be attributed to its potential role in epigenetic regulation, which may influence genetic expression.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"14"},"PeriodicalIF":2.9000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurotoxicity Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12640-025-00735-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Neural tube defects (NTDs) are severe congenital anomalies affecting 1-2 infants per 1000 births, and are influenced by genetic and environmental factors, with DNA hypomethylation and methylation cycle suppression being key causes. In our earlier investigation, decitabine (DCT) caused multiple NTDs in embryonic zebrafish, supporting this hypothesis. Recent research has emphasized the importance of myo-inositol (MI) in embryonic development and its efficacy in reducing the risk of neural tube defects, even in cases resistant to folate. We aimed to examine the effect of MI on DCT-induced NTDs in an embryonic zebrafish model. The embryos were exposed to 1 mM DCT alone, 50 µM MI with 1 mM DCT, 100 µM MI with 1 mM DCT, and a control group for comparison. The development, hatching, mortality rates, neural tube malformations, and neural tube patterning of developing embryos were monitored and recorded. Exposure to MI significantly reduced the incidence of NTDs in developing embryos. At concentrations of 50 µM and 100 µM, MI provided 35% and 30% protection against DCT-induced neural tube malformation, respectively. Multiple NTDs were significantly reduced in the MI groups, with 1 mM DCT causing 95% defects, 50 µM MI with 1 mM DCT causing 50%, and 100 µM MI with 1 mM DCT causing 55% defects. The DCT-induced hatching delay was also reversed by MI treatment. Alizarin red staining and histopathological observations supported these observations. In the context of neural tube development, the protective effects of MI against DCT-induced NTDs could be attributed to its potential role in epigenetic regulation, which may influence genetic expression.
神经管缺陷(Neural tube defects, NTDs)是一种严重的先天性畸形,每1000个新生儿中有1-2例,受遗传和环境因素的影响,其中DNA低甲基化和甲基化周期抑制是主要原因。在我们早期的研究中,地西他滨(DCT)在胚胎斑马鱼中引起了多个NTDs,支持了这一假设。最近的研究强调了肌醇(MI)在胚胎发育中的重要性,以及它在降低神经管缺陷风险方面的功效,即使在对叶酸有抵抗力的情况下也是如此。我们的目的是在胚胎斑马鱼模型中研究心肌梗死对dct诱导的NTDs的影响。胚胎单独暴露于1 mM DCT、50µM MI + 1 mM DCT、100µM MI + 1 mM DCT,并作为对照组进行比较。对胚胎的发育、孵化、死亡率、神经管畸形和发育中的神经管模式进行了监测和记录。暴露于心肌梗死显著降低了发育中的胚胎中NTDs的发生率。在浓度为50µM和100µM时,MI对dct诱导的神经管畸形的保护作用分别为35%和30%。在MI组中,多个NTDs显著减少,1 mM DCT组的缺陷发生率为95%,50µM MI组的缺陷发生率为50%,100µM MI组的缺陷发生率为55%。心肌梗死治疗也逆转了dct诱导的孵化延迟。茜素红染色和组织病理学观察支持这些观察结果。在神经管发育的背景下,心肌梗死对dct诱导的NTDs的保护作用可能归因于其在表观遗传调控中的潜在作用,这可能影响遗传表达。
期刊介绍:
Neurotoxicity Research is an international, interdisciplinary broad-based journal for reporting both basic and clinical research on classical neurotoxicity effects and mechanisms associated with neurodegeneration, necrosis, neuronal apoptosis, nerve regeneration, neurotrophin mechanisms, and topics related to these themes.
Published papers have focused on:
NEURODEGENERATION and INJURY
Neuropathologies
Neuronal apoptosis
Neuronal necrosis
Neural death processes (anatomical, histochemical, neurochemical)
Neurodegenerative Disorders
Neural Effects of Substances of Abuse
NERVE REGENERATION and RESPONSES TO INJURY
Neural Adaptations
Neurotrophin mechanisms and actions
NEURO(CYTO)TOXICITY PROCESSES and NEUROPROTECTION
Excitatory amino acids
Neurotoxins, endogenous and synthetic
Reactive oxygen (nitrogen) species
Neuroprotection by endogenous and exogenous agents
Papers on related themes are welcome.