Neurotoxicology and teratology最新文献_第4页

Effects of bisphenol-a on vasopressin regulating synaptic plasticity of hippocampus 双酚a对加压素调节海马突触可塑性的影响。

IF 2.8 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-07-01 DOI: 10.1016/j.ntt.2025.107531

Xiaohong Xu, Jinshan Wang, Yani Yang

The neuropeptide arginine vasopressin (AVP) plays an important role in the hippocampus by regulating neuronal excitability, synaptic plasticity, and other processes. Activity of AVP is regulated by sex hormones. The present study investigated the effects of bisphenol-A (BPA), a environmental endocrine disruptor, on AVP regulating synaptic plasticity of hippocamus. AVP at 10–100 nM significantly increased the dendrite complexity and dendrite spine density of hippocampal neurons in vitro, which was partially eliminated by AVP receptor 1a (V1aR) antagonist (RG7713) or oxytocin receptor (OTR) antagonist (L368–899). BPA at 10 nM increased neuronal dendritic complexity and spine density, which was partially eliminated by estrogen receptor (ERs) antagonist (ICI182,780) but completely abolished by antagonist of both ERs and ERRγ (Tamoxifen). BPA at 10 nM did not affect the effect of AVP (100 nM) on the dendrite complexity and spine density, but eliminated the promoting effects of DHT + AVP on the dendritic complexity. BPA at 1000 nM not only inhibited the dendritic complexity but also eliminated the promoting effects of AVP, 17β-estradiol (17β-E₂) + AVP, and 11-ketodihydrotestosterone (DHT) + AVP on the dendritic complexity. In addition, BPA at 1000 nM down-regulated the levels of V1aR and OTR protein expressions. Meanwhile, BPA at 10 nM promoted the maintenance of LTP of CA2 in the hippocampal slices, but co-treatment of BPA eliminated the effect of 17β-E₂ or DHT on LTP. BPA (10 nM) did not affect the promotion of long-term potentiation (LTP) by AVP, but eliminated the promotion of LTP by DHT + AVP. These results suggest that BPA at nanomoles levels affected AVP regulating modification of dendrite morphology and synaptic plasticity of hippocampus mainly by disrupting the effects of 17β-E₂ and/or DHT on AVP activity.

神经肽精氨酸加压素（AVP）在海马中通过调节神经元兴奋性、突触可塑性等过程发挥重要作用。AVP的活性受性激素的调节。本研究探讨了环境内分泌干扰物双酚a （BPA）对AVP调节海马突触可塑性的影响。AVP 10-100 nM显著增加体外海马神经元树突复杂性和树突棘密度，AVP受体1a （V1aR）拮抗剂（RG7713）或催产素受体（OTR）拮抗剂（L368-899）可部分消除AVP复杂性和树突棘密度。10 nM BPA增加了神经元树突复杂性和脊柱密度，雌激素受体（er）拮抗剂（ici182780）部分消除了这一作用，但雌激素受体和ERRγ拮抗剂（他莫昔芬）完全消除了这一作用。10 nM BPA不影响AVP（100 nM）对树突复杂性和脊柱密度的影响，但消除了DHT + AVP对树突复杂性的促进作用。1000 nM BPA不仅能抑制树突复杂性，还能消除AVP、17β-雌二醇（17β-E2） + AVP和11-酮二氢睾酮（DHT） + AVP对树突复杂性的促进作用。此外，BPA在1000 nM时下调了V1aR和OTR蛋白的表达水平。同时，BPA在10 nM时促进了海马片CA2对LTP的维持，但BPA联合处理消除了17β-E2或DHT对LTP的影响。BPA（10 nM）不影响AVP对长期增强（LTP）的促进作用，但消除了DHT + AVP对LTP的促进作用。这些结果表明，纳米摩尔水平的BPA主要通过破坏17β-E2和DHT对AVP活性的影响来影响AVP，从而调节海马树突形态的改变和突触的可塑性。

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引用次数: 0

The East Palestine train derailment: A complex environmental disaster 东巴勒斯坦火车出轨：一场复杂的环境灾难。

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-07-01 DOI: 10.1016/j.ntt.2025.107522

Lynn T. Singer , Fredrick Schumacher , James Fabisiak , Laura J. Dietz , Timothy Ciesielski

This symposium, The East Palestine Train Derailment: A Complex Environmental Disaster, brought together scientists whose research represented initial scientific responses to the community health impacts of the chemical exposures incurred from a disastrous train derailment and subsequent combustion in East Palestine, Ohio in February, 2023. This derailment and burn led to multiple complex toxic exposures to air, soil and water, including vinyl chloride and butyl acrylate. Presenters described the multi-university consortium formed to assist with developing and communicating data-informed summaries to the affected community. Presenters also reported on the immediate health sequelae experienced by the community and the stress and uncertainty regarding long term effects. Plans were reported for several pilot studies funded by the National Institute on Environmental Health Sciences in immediate response to the disaster. Fredrick Schumacher, PhD outlined the aims of The Healthy Futures Research Study: Linking Somatic Mutation Rate with Baseline Exposure in East Palestine that plans to use somatic mutation rate (SMR) to measure the biological impact of environmental exposures based on proximity to the train derailment and residents’ clinical symptomatology. James Fabisiak, PhD shared plans for their study, East Palestine Community-Engaged Environmental Exposure, Health Data, and Biospecimen Bank that will measure chemical contaminants in indoor air and water in homes, monitor liver damage in residents and identify parents’ concerns about children’s health and development. As part of that study, Laura Dietz, PhD noted the major psychosocial stressors experienced by the community, particularly the psychological effects on children which the study will try to identify through parental report. Timothy Ciesielski, MD, PhD summarized the difficulties of drawing conclusions related to health and safety risk from the toxicants released through currently available government databases and his experience trying to provide the community with reliable and valid information in the context of working across state lines and multiple state and federal agencies.

本次研讨会题为“东巴勒斯坦火车脱轨：一场复杂的环境灾难”，汇集了科学家，他们的研究代表了对2023年2月俄亥俄州东巴勒斯坦灾难性火车脱轨和随后燃烧造成的化学品暴露对社区健康影响的初步科学反应。这种脱轨和燃烧导致多种复杂的有毒物质暴露于空气、土壤和水中，包括氯乙烯和丙烯酸丁酯。发言者介绍了为协助制定和向受影响社区传播数据知情摘要而组成的多所大学联盟。发言者还报告了社区所经历的直接健康后遗症以及长期影响的压力和不确定性。据报告，由国家环境健康科学研究所资助的几项试点研究计划是为了立即对灾难作出反应。Fredrick Schumacher博士概述了健康未来研究的目标：将东巴勒斯坦的体细胞突变率与基线暴露联系起来，该研究计划使用体细胞突变率（SMR）来测量基于火车脱轨和居民临床症状的环境暴露的生物学影响。James Fabisiak博士分享了他们的研究计划，东巴勒斯坦社区参与的环境暴露，健康数据和生物标本库，将测量室内空气和家庭水中的化学污染物，监测居民的肝损伤，并确定父母对儿童健康和发展的担忧。作为该研究的一部分，劳拉·迪茨博士指出了社区所经历的主要社会心理压力源，特别是对儿童的心理影响，该研究将试图通过父母报告来确定。Timothy Ciesielski，医学博士，总结了通过目前可用的政府数据库从释放的有毒物质中得出与健康和安全风险相关的结论的困难，以及他在跨州界和多个州和联邦机构工作的背景下试图为社区提供可靠和有效信息的经验。

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引用次数: 0

Salvianolic acid A enhances sedative effect of diazepam through the GABAergic pathway: In vivo, molecular docking, and pharmacokinetics approaches 丹酚酸A通过gaba能途径增强地西泮的镇静作用：体内、分子对接和药代动力学方法

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-06-25 DOI: 10.1016/j.ntt.2025.107517

Imam Hossen Rakib , Mohd Shahnawaz Khan , Arusha Ayub , Md. Sakib Al Hasan , Mohammed Alfaifi , Md. Shimul Bhuia , Emon Mia , Noshin Tasnim Yana , Md. Nasimul Haque Shipon , Muhammad Torequl Islam

Salvianolic acid A (SAL A), a polyphenolic compound derived from Salvia miltiorrhiza, exhibits several neuroprotective effects, but its sedative potential is unexamined. This study explores the sedative effects of SAL A and its potential to modulate the impacts of diazepam (DZP) in a thiopental sodium (TS)-induced sleep model in Swiss albino mice. Mice received intraperitoneal (i.p.) doses of SAL A (5 and 10 mg/kg) and DZP (2 mg/kg), followed by TS (20 mg/kg), with sleep latency and duration recorded. Molecular docking and in silico analyses evaluated SAL A’s interaction with the GABA_A receptor (α1 and β2 subunits) (PDB ID: 6X3X) and its pharmacokinetic properties. Results revealed that SAL A significantly (p < 0.05) reduced sleep latency and prolonged sleep duration dose-dependently, with 10 mg/kg showing the strongest effect (latency: 14.29 ± 3.09 min; duration: 175.71 ± 18.97 min; Cohen's d = 4.37 and 1.60, respectively). Combined therapy with SAL A-10 and DZP-2 synergistically enhanced sleep duration, with the highest effect sizes observed (d = 5.45 for latency; 4.36 for duration). Molecular docking studies revealed that SAL A showed similar binding affinity (−8.7 kcal/mol) with 6X3X, comparable to DZP. SAL A also exhibited favorable pharmacokinetic properties and low toxicity. These findings suggest SAL A as a potential novel sedative agent with synergistic effects alongside DZP. However, SAL A's poor blood-brain barrier permeability and need for structural optimization highlight the necessity for future mechanistic studies, enhanced delivery methods, and clinical validation to confirm its therapeutic potential for sleep disorders.

丹酚酸A （Salvianolic acid A, SAL A）是一种从丹参中提取的多酚类化合物，具有多种神经保护作用，但其镇静作用尚未得到证实。本研究探讨了SAL A的镇静作用及其在硫贲妥钠（TS）诱导的瑞士白化小鼠睡眠模型中调节地西泮（DZP）影响的潜力。小鼠腹腔注射5、10 mg/kg的SAL A和2 mg/kg的DZP，然后注射20 mg/kg的TS，记录睡眠潜伏期和持续时间。分子对接和计算机分析评估了SAL A与GABAA受体（α1和β2亚基）（PDB ID: 6X3X）的相互作用及其药代动力学性质。结果显示SAL显著(p <；0.05)减少睡眠潜伏期，延长睡眠持续时间，以10 mg/kg效果最强(潜伏期：14.29±3.09 min；持续时间：175.71±18.97分钟；Cohen’s d分别= 4.37和1.60)。与SAL A-10和DZP-2联合治疗可协同延长睡眠时间，观察到的效应值最高(潜伏期d = 5.45；4.36（持续时间）。分子对接研究表明，SAL A与6X3X具有相似的结合亲和力（−8.7 kcal/mol），与DZP相当。SAL A还表现出良好的药动学特性和低毒性。这些发现提示SAL A是一种潜在的新型镇静剂，与DZP具有协同作用。然而，SAL A较差的血脑屏障渗透性和对结构优化的需求突出了未来机制研究、增强给药方法和临床验证的必要性，以确认其治疗睡眠障碍的潜力。

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引用次数: 0

Metal exposure in Brazilian children of waste pickers from the largest open garbage dump in Latin America: Use of deciduous teeth as biomarker 拉丁美洲最大露天垃圾场拾捡者对巴西儿童的金属暴露：使用乳牙作为生物标志物

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-06-25 DOI: 10.1016/j.ntt.2025.107516

Andrea M. Dantas , Eliude B. Gomes , Raquel F. Gerlach , Airton C. Martins , Tara R. Zolnikov , Aline M. Susuki , Ana C.B. Bezerra , Fernando Barbosa Jr , Michael Aschner , Mariana R. Urbano , Monica M.B. Paoliello , Vanessa R.N. Cruvinel

Environmental exposures to metals is a concern for public health, due to their association with various adverse health outcomes, especially in children. The aim of this study was to analyze 21 metals (V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Ag, Cd, Ba, Ti, Pb, U, Sn, Mo, Ce, La, and Th) in deciduous teeth of waste pickers' children from an open garbage dump region (Estrutural region- Group 1), and compare them with children living in two other regions in Brasilia (Ceilandia – Group 2, and Plano Piloto – Group 3). Three hundred and two children participated in the study, and a single deciduous whole tooth (dentine plus enamel) was analyzed from each child. Socio-demographic variables, breastfeeding time, visits to the dentist, drinking water consumption, among others, were obtained through a questionnaire provided to the parents or guardians of the children. Metal analyses were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Significantly higher concentrations of V, Co, Cu, and As were found in children from G1, where most parents were waste pickers, compared to the other two regions (p < 0.01). Pb and Cd concentrations were significantly higher in children from G2 and G3 compared with G1 (p < 0.01). Significantly higher levels of Cr, Mn, Zn and Se were found in children from G2 (p < 0.01), where residents also have very low income, analogous to G1. We found a trend towards an increase in metal concentrations in incisor compared to canine and molar teeth of children in all three groups. This study provides novel data and reinforces the use of deciduous teeth as potential matrix for biomonitoring children's metal exposures.

环境暴露于金属与各种不利的健康后果，特别是儿童的健康后果有关，因此是一个令人关切的公共健康问题。本研究的目的是分析一个露天垃圾场（e结构性区- 1组）拾捡者儿童乳牙中的21种金属（V、Cr、Mn、Co、Ni、Cu、Zn、As、Se、Rb、Ag、Cd、Ba、Ti、Pb、U、Sn、Mo、Ce、La和Th），并与生活在巴西ilia其他两个地区（Ceilandia - 2组和Plano Piloto - 3组）的儿童进行比较。312名儿童参加了这项研究，并对每个儿童的一颗乳牙（牙本质加牙釉质）进行了分析。社会人口变量、母乳喂养时间、看牙医次数、饮水消耗等都是通过向儿童的父母或监护人提供的调查表获得的。金属分析采用电感耦合等离子体质谱法（ICP-MS）。与其他两个地区相比，G1儿童中发现的V、Co、Cu和As浓度明显较高，因为该地区大多数父母都是拾捡垃圾的人(p <；0.01)。G2和G3患儿的铅和镉浓度明显高于G1 (p <；0.01)。G2组儿童的Cr、Mn、Zn和Se水平显著升高(p <；0.01)，那里的居民收入也很低，类似于G1。我们发现，与所有三组儿童的犬齿和磨牙相比，门牙中的金属浓度有增加的趋势。本研究提供了新的数据，并加强了乳牙作为儿童金属暴露生物监测的潜在基质的使用。

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引用次数: 0

Effects of N-acetylcysteine after repeated exposure to ethanol in memory and neurotransmission in zebrafish 反复暴露于乙醇后n -乙酰半胱氨酸对斑马鱼记忆和神经传递的影响。

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-06-12 DOI: 10.1016/j.ntt.2025.107508

Daiana Alves Spilere, Guilherme Lodetti, Ana Carolina Salvador de Farias, Amanda Gomes Teixeira, Eduardo Ronconi Dondossola, Eduardo Pacheco Rico

Introduction

In the brain, alcohol metabolites alter the functioning of several neurotransmission systems, such as glutamatergic and cholinergic, in addition to impairing memory and learning. Medications for Alcohol Use Disorders (AUD) cause adverse effects and contraindications. N-acetylcysteine (NAC) has been shown to protect memory and restore acetylcholinesterase (AChE) levels. Additionally, it functions as an antioxidant that works alongside glutathione, which is associated with the glutamatergic synapse. In this context, the current research aimed to examine the neuroprotective effects of NAC in animals that underwent repeated ethanol exposure (REE), along with the impacts on memory and the cholinergic and glutamatergic signaling pathways in zebrafish.

Methods

The animals were exposed to 1 % ethanol for 8 days for 20 min daily. They received treatment with NAC after the eighth exposure to ethanol for 10 or 60 min. Euthanasia occurred 24 h after the last exposure. Inhibitory avoidance and object recognition tests were performed. Also, the choline acetyltransferase (ChAT) enzyme activities, AChE activity, and glutamate uptake were evaluated.

Results

The results show a significant AChE activity increase in the REE group and a decrease in those exposed to alcohol and treated with NAC for 10 min. No significant differences were found regarding ChAT activity. REE significantly reduced glutamate uptake. All groups except the ethanol group acquired aversive memory in inhibitory avoidance tests. Only the NAC-treated group demonstrated longer new object exploration in the recognition test. The study indicates that REE affects AChE, glutamate uptake, and aversive memory and that a single NAC treatment can mitigate these effects. These findings enhance the understanding of REE mechanisms and NAC's protective properties against ethanol-induced damage in zebrafish.

简介：在大脑中，酒精代谢物除了损害记忆和学习能力外，还会改变几种神经传递系统的功能，如谷氨酸能和胆碱能。治疗酒精使用障碍（AUD）的药物会导致不良反应和禁忌症。n -乙酰半胱氨酸（NAC）已被证明具有保护记忆和恢复乙酰胆碱酯酶（AChE）水平的作用。此外，它作为一种抗氧化剂，与谷胱甘肽一起作用，谷胱甘肽与谷氨酸能突触有关。在此背景下，目前的研究旨在研究NAC对反复乙醇暴露（REE）的动物的神经保护作用，以及对斑马鱼记忆和胆碱能和谷氨酸能信号通路的影响。方法：1 %乙醇浸泡8 天，每天20 min。他们在第八次暴露于乙醇10或60 分钟后接受NAC治疗。安乐死发生在最后一次接触后24 小时。进行了抑制性回避和目标识别测试。测定了胆碱乙酰转移酶（ChAT）活性、乙酰胆碱酯交换酶（AChE）活性和谷氨酸摄取。结果：结果显示，REE组乙酰胆碱酯酶活性显著增加，暴露于酒精和NAC治疗10 min组乙酰胆碱酯酶活性降低。在ChAT活性方面没有发现显著差异。REE显著降低谷氨酸摄取。在抑制回避试验中，除乙醇组外，其余各组均获得了厌恶记忆。只有nac处理组在识别测试中表现出更长时间的新物体探索。研究表明REE影响乙酰胆碱酯酶、谷氨酸摄取和厌恶记忆，单一NAC治疗可以减轻这些影响。这些发现增强了对REE机制和NAC对斑马鱼乙醇损伤的保护作用的理解。

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引用次数: 0

TREM2 inhibits LPS-induced pyroptosis and inflammation by promoting mitophagy via SYK in BV2 cells TREM2通过SYK促进BV2细胞的有丝分裂，从而抑制lps诱导的焦亡和炎症。

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-05-31 DOI: 10.1016/j.ntt.2025.107500

Wenwen Jiang , Xixin Fan , Hui Wu , Jiankang Song , Chunhe Yang , Zhanzhi Zhao

Neuroinflammation is a critical factor in the pathogenesis of postoperative cognitive dysfunction (POCD). Maintaining microglial homeostasis is vital for regulating neuroinflammation, as microglial cell death can trigger an inflammatory response within the central nervous system. The triggering receptor expressed on myeloid cells 2 (TREM2) plays an essential role in supporting cell survival and modulating microglial-driven neuroinflammation. Our previous study indicated that TREM2 overexpression exerts protective effects against neuroinflammation and cognitive deficits in aged mice. However, the precise mechanisms by which TREM2 functions in microglia remain unclear. Consequently, this study aimed to examine the role of TREM2 in lipopolysaccharide (LPS)-induced cell death and neuroinflammation in BV2 cells. This research showed that TREM2 reduces LPS-induced nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis and the subsequent release of inflammatory factors through western blot analysis, flow cytometry, and enzyme-linked immunosorbent assay. Recent research has suggested that the loss of spleen tyrosine kinase (SYK), a downstream receptor kinase of TREM2 in microglia, results in exacerbated neuroinflammatory disease. This study further demonstrated that SYK activation via TREM2 treatment exerts neuroprotective effects by mitigating LPS-induced mitochondrial membrane potential damage, facilitating mitophagy, and inhibiting NLRP3-mediated pyroptosis in BV2 cells. Conversely, SYK inhibition by R406 led to microglial cell death and aggravated neuroinflammation, thereby reducing the neuroprotective effects of TREM2. Our findings indicate that TREM2 and SYK mitigate the inflammatory response in LPS-induced BV2 microglia and interfere with pyroptosis by enhancing mitophagy. These findings suggest that TREM2 and SYK may be valuable therapeutic targets for neuroinflammation.

神经炎症是术后认知功能障碍（POCD）发病的关键因素。维持小胶质细胞的稳态对于调节神经炎症至关重要，因为小胶质细胞的死亡可以引发中枢神经系统的炎症反应。髓样细胞2上表达的触发受体（TREM2）在支持细胞存活和调节小胶质细胞驱动的神经炎症中起重要作用。我们之前的研究表明，TREM2过表达对老年小鼠的神经炎症和认知缺陷具有保护作用。然而，TREM2在小胶质细胞中起作用的确切机制尚不清楚。因此，本研究旨在研究TREM2在脂多糖（LPS）诱导的BV2细胞死亡和神经炎症中的作用。本研究通过western blot分析、流式细胞术和酶联免疫吸附实验表明，TREM2可以减少lps诱导的核苷酸结合寡聚结构域样受体蛋白3 （NLRP3）介导的焦亡和随后的炎症因子释放。最近的研究表明，脾酪氨酸激酶（SYK）是小胶质细胞中TREM2的下游受体激酶，其缺失可导致神经炎症性疾病加重。本研究进一步证明，通过TREM2处理激活SYK可减轻lps诱导的线粒体膜潜在损伤，促进线粒体自噬，抑制nlrp3介导的BV2细胞焦亡，从而发挥神经保护作用。相反，R406抑制SYK导致小胶质细胞死亡和神经炎症加重，从而降低TREM2的神经保护作用。我们的研究结果表明，TREM2和SYK可以减轻lps诱导的BV2小胶质细胞的炎症反应，并通过增强线粒体自噬来干扰焦亡。这些发现表明TREM2和SYK可能是神经炎症的有价值的治疗靶点。

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引用次数: 0

Pathways from prenatal alcohol exposure to adult working memory deficit 从产前酒精暴露到成人工作记忆缺陷的途径

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-05-01 DOI: 10.1016/j.ntt.2025.107483

Lynn Singer , Elizabeth Schultheis , Jeffrey Albert , June-yung Kim , Sonia Minnes , Meeyoung Min

引用次数: 0

Identifying teratogens: Challenges and opportunities 识别致畸物：挑战与机遇

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology

Pub Date : 2025-05-01 DOI: 10.1016/j.ntt.2025.107453

Sonja A. Rasmussen