Neurotoxicology最新文献_第4页

Exposure to an environmentally representative mixture of polybrominated diphenyl ethers (PBDEs) alters zebrafish neuromuscular development 接触具有环境代表性的多溴联苯醚混合物会改变斑马鱼的神经肌肉发育

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-28 DOI: 10.1016/j.neuro.2024.10.009

Alec McDermott, Cécilia Bernier, Vanessa Piché, Isabelle Plante , Shunmoogum A. Patten

Polybrominated diphenyl ethers (PBDEs) are a prevalent group of brominated flame retardants (BFRs) added to several products such as electronics, plastics, and textiles to reduce their flammability. They are reported as endocrine disruptors and neurodevelopmental toxicants that can accumulate in human and wildlife tissues, thus making their ability to leach out of products into the environment a great cause for concern. In this study, zebrafish (Danio rerio) embryos and larvae were exposed to a wide concentration range (1.5, 15, 150 and 300 pM) of a PBDE mixture from one to six days post-fertilization (dpf). Hatching rates, mortality and general morphology were assessed during the exposure period. A delay in hatching was observed at the two highest PBDEs concentrations and mortality rate increased at 6 dpf. By 4 dpf, larvae exposed to 150 pM and 300 pM PBDEs developed an upcurved phenotype. Analysis of motor behavior at 6 dpf revealed that PBDE exposure acutely reduced locomotion. To further analyze these motor deficits, we assessed the neural network density and motor neuron and neuromuscular junctions (NMJ) development by immunostaining and imaging. Acetylated α-tubulin staining revealed a significant loss of neurons in a dose-dependent manner. Synaptic vesicle protein 2 (SV2) and ⍺-bungarotoxin (⍺-BTX) staining revealed a similar pattern, with a significant loss of SV2 and nicotinic acetylcholine receptors, thus preventing the colocalization of presynaptic neurons with postsynaptic neurons. Consistent with these results, the presence of cleaved caspase-3 and acridine orange positive cells showed increased cell death in zebrafish larvae exposed to PBDEs. Our results suggest that exposure to PBDEs leads to deficits in the zebrafish neuromuscular system through neuron death, inducing morphological and motor deficiencies throughout their development. They provide valuable insight into the neurotoxic effects of PBDEs, further highlighting the relevance of the zebrafish model in toxicological studies.

多溴联苯醚（PBDEs）是一组普遍存在的溴化阻燃剂（BFRs），被添加到电子产品、塑料和纺织品等多种产品中，以降低其易燃性。据报道，它们是内分泌干扰物和神经发育毒物，可在人体和野生动物组织中蓄积，因此，它们从产品中渗出进入环境的能力非常令人担忧。在这项研究中，斑马鱼（Danio rerio）的胚胎和幼虫在受精后 1 到 6 天（dpf）期间暴露于浓度范围很广（1.5、15、150 和 300 pM）的多溴联苯醚混合物中。在暴露期间，对孵化率、死亡率和总体形态进行了评估。在多溴联苯醚浓度最高的两种情况下，幼虫的孵化出现延迟，而在受精后 6 dpf 死亡率有所上升。到 4 dpf 时，暴露于 150 pM 和 300 pM 多溴联苯醚的幼虫出现了上弯表型。对 6 dpf 幼虫运动行为的分析表明，暴露于多溴联苯醚的幼虫运动能力会急剧下降。为了进一步分析这些运动缺陷，我们通过免疫染色和成像技术评估了神经网络密度以及运动神经元和神经肌肉接头（NMJ）的发育情况。乙酰化α-微管蛋白染色显示，神经元以剂量依赖的方式显著减少。突触小泡蛋白 2（SV2）和银杏毒素（BTX）染色显示了类似的模式，SV2 和烟碱乙酰胆碱受体显著丢失，从而阻止了突触前神经元与突触后神经元的共定位。与这些结果一致的是，暴露于多溴联苯醚的斑马鱼幼体中出现的裂解的 Caspase-3 和吖啶橙阳性细胞表明细胞死亡增加。我们的研究结果表明，暴露于多溴联苯醚会通过神经元死亡导致斑马鱼神经肌肉系统缺陷，并在其整个发育过程中诱发形态和运动缺陷。这些结果为了解多溴联苯醚的神经毒性效应提供了宝贵的信息，进一步突出了斑马鱼模型在毒理学研究中的相关性。

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引用次数: 0

Manifestation of polystyrene microplastic accumulation in brain with emphasis on morphometric and histopathological changes in limbic areas of Swiss albino mice 聚苯乙烯微塑料在大脑中积累的表现，重点是瑞士白化小鼠边缘区的形态计量学和组织病理学变化。

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-18 DOI: 10.1016/j.neuro.2024.10.008

Manjyot Kaur, Anju Sharma, Placheril John, Pradeep Bhatnagar

The widespread problem of microplastic (MP) contamination is becoming a major threat to the globe. Although most of the research to date has concentrated on the physiological impacts of MPs exposure, a relatively new field of study is beginning to examine its effects on the behaviour and limbic regions of the brain. In this study, exposure to polystyrene MPs (PS-MPs) for acute and sub-chronic durations negatively affected cognition and induced anxiety-like behaviour in mice. PS-MPs were detected in vital organs of mice, including the brain, which induced neurobehavioural and pathological changes in the limbic system. Furthermore, morphometric analysis revealed a significant decrease in the total cell count in the Dentate Gyrus (DG) and Cornu Ammonis (CA) regions of the hippocampus. Signs of neuronal injury and dystrophic changes were observed in the cortex, amygdala, and hypothalamus, potentially affecting anxiety and fear responses. Our study thus provides insight into the effect of PS-MPs on the neurobiology of the brain’s limbic system and related behavioural alterations.

广泛存在的微塑料（MP）污染问题正成为全球面临的主要威胁。尽管迄今为止的大部分研究都集中在接触 MPs 对生理的影响上，但一个相对较新的研究领域正在开始研究 MPs 对行为和大脑边缘区域的影响。在这项研究中，急性和亚慢性接触聚苯乙烯多氯联苯（PS-MPs）会对小鼠的认知能力产生负面影响，并诱发焦虑行为。在小鼠的重要器官（包括大脑）中都检测到了 PS-MPs，它诱发了边缘系统的神经行为和病理变化。此外，形态计量分析显示，海马齿状回（Dentate Gyrus，DG）和海马角（Cornu Ammonis，CA）区域的细胞总数显著减少。在大脑皮层、杏仁核和下丘脑中观察到了神经元损伤和萎缩变化的迹象，这可能会影响焦虑和恐惧反应。因此，我们的研究有助于深入了解 PS-MPs 对大脑边缘系统神经生物学和相关行为改变的影响。

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引用次数: 0

Neuroprotective effect of empagliflozin against doxorubicin-induced chemobrain in rats: Interplay between SIRT-1/MuRF-1/PARP-1/NLRP3 signaling pathways and enhanced expression of miRNA-34a and LncRNA HOTAIR empagliflozin对多柔比星诱导的大鼠化疗脑的神经保护作用：SIRT-1/MuRF-1/PARP-1/NLRP3信号通路与miRNA-34a和LncRNA HOTAIR表达增强之间的相互作用。

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-18 DOI: 10.1016/j.neuro.2024.10.006

Merihane M. Nasr , Sara A. Wahdan , Reem N. El-Naga , Rania M. Salama

Chemobrain, a challenging side effect of doxorubicin (DOX)-based chemotherapy, impairs cognitive abilities in cancer survivors. DOX triggers chemobrain via oxidative stress, leading to inflammation and apoptosis. Empagliflozin (EMPA), a sodium glucose co-transporter-2 inhibitor, demonstrated neuroprotective effects by reducing reactive oxygen species (ROS) and inflammation, but its protective mechanisms against DOX-induced chemobrain is not fully known. Thus, this study aimed to investigate EMPA’s neuroprotective effects on DOX-induced chemobrain in rats and to uncover the underlying protective mechanisms. Fifty male Wistar rats were divided into control, EMPA, DOX (2 mg/kg, IP, once/week for 4 weeks), and two treated groups (DOX+ EMPA 5 and 10 mg/kg/day, PO, for 4 weeks). Behavioral tests showed improved memory, motor performance, and reduced anxiety in EMPA-treated groups compared to DOX, with superior results at the higher dose. Histopathological analysis revealed increased intact neurons in the cortex and hippocampus in EMPA-treated groups, with 346.4 % increase in CA3 (p < 0.0001), 19.1 % in dentate gyrus (p = 0.0006), and 362.6 % in cortex (p < 0.0001) in the high-dose EMPA group. Biochemical investigations of the high-dose EMPA group revealed significant decreases in inflammatory and apoptotic markers (JNK/PARP-1/NLRP3/MuRF-1/FOXO-1), increased SIRT-1 protein expression by 389.9 % (p < 0.0001), and reduced miRNA-34a and LncRNA HOTAIR gene expression (50.4 % and 53.4 % respectively, p < 0.0001) relative to DOX group. Conclusively, EMPA demonstrated superior behavioral and histopathological outcomes particularly at higher dose, positioning it as a promising neuroprotective candidate against DOX-induced chemobrain, possibly through modulating SIRT-1, NF-κb, NLRP3, and oxidative stress pathways.

化脑是以多柔比星（DOX）为基础的化疗所产生的一种具有挑战性的副作用，会损害癌症幸存者的认知能力。DOX 通过氧化应激引发化脑，导致炎症和细胞凋亡。恩格列净（Empagliflozin，EMPA）是一种钠葡萄糖协同转运体-2抑制剂，通过减少活性氧（ROS）和炎症表现出神经保护作用，但其对DOX诱导的化脑的保护机制尚不完全清楚。因此，本研究旨在探讨 EMPA 对 DOX 诱导的大鼠化学脑的神经保护作用，并揭示其潜在的保护机制。50 只雄性 Wistar 大鼠被分为对照组、EMPA 组、DOX 组（2 毫克/千克，IP，每周一次，连续 4 周）和两个治疗组（DOX+ EMPA 5 毫克/千克/天和 10 毫克/千克/天，PO，连续 4 周）。行为测试表明，与 DOX 相比，EMPA 治疗组的记忆力和运动表现均有所改善，焦虑情绪也有所减轻，而高剂量的 EMPA 治疗效果更佳。组织病理学分析表明，EMPA治疗组大脑皮层和海马中的完整神经元增加了，高剂量EMPA组CA3增加了346.4%（p < 0.0001），齿状回增加了19.1%（p = 0.0006），大脑皮层增加了362.6%（p < 0.0001）。与DOX组相比，大剂量EMPA组的生化检查显示炎症和细胞凋亡标志物（JNK/PARP-1/NLRP3/MuRF-1/FOXO-1）显著减少，SIRT-1蛋白表达增加389.9%（p < 0.0001），miRNA-34a和LncRNA HOTAIR基因表达减少（分别为50.4%和53.4%，p < 0.0001）。总之，EMPA表现出卓越的行为和组织病理学结果，尤其是在较高剂量时，它可能通过调节SIRT-1、NF-κb、IL-1β和氧化应激途径，对DOX诱导的化疗脑起到保护神经的作用。

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引用次数: 0

Investigating tributyltin's toxic effects: Intestinal barrier and neuroenteric disruption in rat’s jejunum 研究三丁基锡的毒性作用：大鼠空肠的肠道屏障和神经肠功能紊乱

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-11 DOI: 10.1016/j.neuro.2024.10.004

I.C.C.S. Oliveira , G.P. Marinsek , A.R.N. Gonçalves , B.S. Lopes , L.V.B. Correia , R.C.B. Da Silva , I.B. Castro , R.B. Mari

The expansion of economic activities in coastal areas has significantly increased chemical contamination, leading to major environmental challenges. Contaminants enter the human body through the food chain, particularly via seafood and water consumption, triggering biomagnification and bioaccumulation processes. The gastrointestinal tract (GIT) acts as a selective barrier, protecting against chemical pollutants and maintaining homeostasis through a complex network of cells and immune responses. This study assessed impact of tributyltin (TBT), a highly toxic organometallic compound used in antifouling coatings for ships, on the GIT and myenteric neural plasticity in young rats. TBT exposure leads to histopathological changes, including epithelial detachment and inflammatory foci, especially at lower environmental doses. The study found that TBT causes significant reductions in villi height, increases in goblet cells and intraepithelial lymphocytes, and disrupts the myenteric plexus, with higher densities of extraganglionic neurons in exposed animals.

沿海地区经济活动的扩展大大增加了化学污染，导致重大环境挑战。污染物通过食物链进入人体，特别是通过海产品和水的消费，引发生物放大和生物累积过程。胃肠道（GIT）是一道选择性屏障，通过复杂的细胞和免疫反应网络保护人体免受化学污染物的侵害并维持体内平衡。本研究评估了三丁基锡（TBT）对幼鼠胃肠道和肠系膜神经可塑性的影响，三丁基锡是一种剧毒有机金属化合物，用于船舶防污涂层。接触三丁基锡化合物会导致组织病理学变化，包括上皮脱落和炎症病灶，尤其是在环境剂量较低的情况下。研究发现，三丁基锡化合物会导致绒毛高度明显降低、鹅口疮细胞和上皮内淋巴细胞增加，并破坏肠肌丛，使暴露动物的节外神经元密度升高。

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引用次数: 0

Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe 混合金属暴露对颞叶内侧核磁共振成像弥散特征的影响

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-11 DOI: 10.1016/j.neuro.2024.10.005

Eun-Young Lee , Juhee Kim , Janina Manzieri Prado-Rico , Guangwei Du , Mechelle M. Lewis , Lan Kong , Jeff D. Yanosky , Paul Eslinger , Byoung-Gwon Kim , Young-Seoub Hong , Richard B. Mailman , Xuemei Huang

Background

Environmental exposure to metal mixtures is common and may be associated with increased risk for neurodegenerative disorders including Alzheimer’s disease. This study examined associations of mixed metal exposures with medial temporal lobe (MTL) MRI structural metrics and neuropsychological performance.

Methods

Metal exposure history, whole blood metal, MRI R1 (1/T1) and R2* (1/T2*) metrics (estimates of brain Mn and Fe, respectively), and neuropsychological tests were obtained from subjects with/without a history of mixed metal exposure from welding fumes (42 exposed subjects; 31 controls). MTL structures (hippocampus, entorhinal and parahippocampal cortices) were assessed by morphologic (volume or cortical thickness) and diffusion tensor imaging [mean (MD), axial (AxD), radial diffusivity (RD), and fractional anisotropy (FA)] metrics. In exposed subjects, effects of mixed metal exposure on MTL structural and neuropsychological metrics were examined.

Results

Compared to controls, exposed subjects displayed higher MD, AxD, and RD throughout all MTL ROIs (p’s<0.001) with no morphological differences. They also had poorer performance in processing/psychomotor speed, executive, and visuospatial domains (p’s<0.046). Long-term mixed metal exposure history indirectly predicted lower processing speed performance via lower parahippocampal FA (p’s<0.023). Higher entorhinal R1 and whole blood Mn and Cu levels predicted higher entorhinal diffusivity (p’s<0.043) and lower Delayed Story Recall performance (p=0.007).

Discussion

Mixed metal exposure predicted certain MTL structural and neuropsychological features that are similar to those detected in Alzheimer’s disease at-risk populations. These data warrant follow-up as they may illuminate a potential path for environmental exposure to brain changes associated with Alzheimer’s disease-related health outcomes.

背景：环境中接触金属混合物很常见，这可能与包括阿尔茨海默病在内的神经退行性疾病风险增加有关。本研究探讨了混合金属暴露与内侧颞叶（MTL）核磁共振成像结构指标和神经心理学表现之间的关系：方法：从有/无焊接烟尘混合金属暴露史的受试者（42 名暴露受试者；31 名对照组受试者）处获取金属暴露史、全血金属、MRI R1 (1/T1) 和 R2* (1/T2*) 指标（分别为大脑锰和铁的估计值）以及神经心理学测试结果。通过形态学（体积或皮质厚度）和弥散张量成像[平均（MD）、轴向（AxD）、径向扩散率（RD）和分数各向异性（FA）]指标对 MTL 结构（海马、内侧和海马旁皮质）进行了评估。在暴露受试者中，研究了混合金属暴露对 MTL 结构和神经心理学指标的影响：结果：与对照组相比，暴露受试者在所有 MTL ROI 中的 MD、AxD 和 RD 均较高（p's）：混合金属暴露可预测某些 MTL 结构和神经心理学特征，这些特征与阿尔茨海默病高危人群中检测到的特征相似。这些数据值得跟进，因为它们可能揭示了环境暴露导致与阿尔茨海默病相关的大脑变化的潜在路径。

{"title":"Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe","authors":"Eun-Young Lee , Juhee Kim , Janina Manzieri Prado-Rico , Guangwei Du , Mechelle M. Lewis , Lan Kong , Jeff D. Yanosky , Paul Eslinger , Byoung-Gwon Kim , Young-Seoub Hong , Richard B. Mailman , Xuemei Huang","doi":"10.1016/j.neuro.2024.10.005","DOIUrl":"10.1016/j.neuro.2024.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Environmental exposure to metal mixtures is common and may be associated with increased risk for neurodegenerative disorders including Alzheimer’s disease. This study examined associations of mixed metal exposures with medial temporal lobe (MTL) MRI structural metrics and neuropsychological performance.</div></div><div><h3>Methods</h3><div>Metal exposure history, whole blood metal, MRI R1 (1/T1) and R2* (1/T2*) metrics (estimates of brain Mn and Fe, respectively), and neuropsychological tests were obtained from subjects with/without a history of mixed metal exposure from welding fumes (42 exposed subjects; 31 controls). MTL structures (hippocampus, entorhinal and parahippocampal cortices) were assessed by morphologic (volume or cortical thickness) and diffusion tensor imaging [mean (MD), axial (AxD), radial diffusivity (RD), and fractional anisotropy (FA)] metrics. In exposed subjects, effects of mixed metal exposure on MTL structural and neuropsychological metrics were examined.</div></div><div><h3>Results</h3><div>Compared to controls, exposed subjects displayed higher MD, AxD, and RD throughout all MTL ROIs (p’s<0.001) with no morphological differences. They also had poorer performance in processing/psychomotor speed, executive, and visuospatial domains (p’s<0.046). Long-term mixed metal exposure history indirectly predicted lower processing speed performance via lower parahippocampal FA (p’s<0.023). Higher entorhinal R1 and whole blood Mn and Cu levels predicted higher entorhinal diffusivity (p’s<0.043) and lower <em>Delayed Story Recall</em> performance (p=0.007).</div></div><div><h3>Discussion</h3><div>Mixed metal exposure predicted certain MTL structural and neuropsychological features that are similar to those detected in Alzheimer’s disease at-risk populations. These data warrant follow-up as they may illuminate a potential path for environmental exposure to brain changes associated with Alzheimer’s disease-related health outcomes.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"105 ","pages":"Pages 196-207"},"PeriodicalIF":3.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The inhibitory influence of carvacrol on behavioral modifications, brain oxidation, and general inflammation triggered by paraquat exposure through inhalation 香芹酚对吸入百草枯引起的行为改变、大脑氧化和全身炎症的抑制作用。

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-10 DOI: 10.1016/j.neuro.2024.10.003

Reyhaneh Khosravi , Sima Beigoli , Sepideh Behrouz , Sabiheh Amirahmadi , Parisa Sarbaz , Mahmoud Hosseini , Hadi Sarir , Mohammad Hossein Boskabady

The current study investigated how carvacrol (C) can prevent behavioral and brain oxidative changes, along with systemic inflammation caused by inhaled paraquat (PQ). Control rats exposed to saline solution, whereas six rat groups were subjected to PQ aerosols at a concentration of 54 mg/m³ in 16 days. The PQ-exposed groups received saline (PQ group), C at dosages of 20 (C-L) and 80 mg/kg/day (C-H), dexamethasone at a dosage of 0.03 mg/kg/day, pioglitazone at dose of 5 and 10 mg/kg/day (Pio-L and Pio-H), and a combination of C-L + Pio-L. Various parameters were assessed following the end of the treatment duration. There were marked elevation in total and differential white blood cell counts (WBCs), and malondialdehyde levels in the blood, hippocampus, and cerebral tissue but, thiol, superoxide dismutase (SOD), and catalase (CAT) exhibited a notable decrease (p < 0.05 to p < 0.001). The escape delay and traveled distance exhibited enhancement, however, on the probe day, the duration spent in the target quadrant and the time taken to enter the dark room at 3, 24, 48, and 72 hours post an electrical shock, showed a reduction in the PQ group (P<0.05 to P<0.001). Inhaled PQ-induced changes were significantly improved in C, Pio, Dexa, and C-L + Pio-L treated groups (P<0.05 to P<0.001). The effects of C-L + Pio-L on most measured variables were higher than C-L and Pio-L (P<0.05 to P<0.001). C improved PQ-induced changes similar to dexamethasone and C-L showed additive effects when administered in combination with Pio.

本研究探讨了香芹酚（C）如何防止吸入百草枯（PQ）引起的行为和大脑氧化变化以及全身炎症。对照组大鼠吸入生理盐水，而六组大鼠则在16天内吸入浓度为54毫克/立方米的百草枯气溶胶。暴露于 PQ 的各组分别接受生理盐水（PQ 组）、剂量为 20 毫克/千克/天（C-L）和 80 毫克/千克/天（C-H）的 C、剂量为 0.03 毫克/千克/天的地塞米松、剂量为 5 毫克/千克/天和 10 毫克/千克/天的吡格列酮（Pio-L 和 Pio-H）以及 C-L + Pio-L 的组合。治疗结束后，对各种参数进行了评估。血液、海马和脑组织中的白细胞总数和差值以及丙二醛水平明显升高，但硫醇、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）显著下降（p < 0.05 至 p < 0.001）。然而，在探究日，电击后 3、24、48 和 72 小时在目标象限停留的时间和进入暗室的时间在 PQ 组都有所减少（P<0.05 至 P<0.001）。

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引用次数: 0

The enigma of mitochondrial epigenetic alterations in air pollution-induced neurodegenerative diseases 空气污染诱发神经退行性疾病中线粒体表观遗传学改变之谜。

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-05 DOI: 10.1016/j.neuro.2024.10.002

Sayanti Acharyya , Sruthy Hari Kumar , Apoorva Chouksey , Nikita Soni , Nazim Nazeer , Pradyumna Kumar Mishra

The incidence of neurodegenerative diseases is a growing concern worldwide, affecting individuals from diverse backgrounds. Although these pathologies are primarily associated with aging and genetic susceptibility, their severity varies among the affected population. Numerous studies have indicated air pollution as a significant contributor to the increasing prevalence of neurodegeneration. Cohort studies have provided compelling evidence of the association between prolonged exposure to different air toxicants and cognitive decline, behavioural deficits, memory impairment, and overall neuronal health deterioration. Furthermore, molecular research has revealed that air pollutants can disrupt the body's protective mechanisms, participate in neuroinflammatory pathways, and cause neuronal epigenetic modifications. The mitochondrial epigenome is particularly interesting to the scientific community due to its potential to significantly impact our understanding of neurodegenerative diseases' pathogenesis and their release in the peripheral circulation. While protein hallmarks have been extensively studied, the possibility of using circulating epigenetic signatures, such as methylated DNA fragments, miRNAs, and genome-associated factors, as diagnostic tools and therapeutic targets requires further groundwork. The utilization of circulating epigenetic signatures holds promise for developing novel prognostic strategies, creating paramount point-of-care devices for disease diagnosis, identifying therapeutic targets, and developing clinical data-based disease models utilizing multi-omics technologies and artificial intelligence, ultimately mitigating the threat and prevalence of neurodegeneration.

神经退行性疾病的发病率在全球范围内日益增长，影响着不同背景的人群。虽然这些病症主要与衰老和遗传易感性有关，但其严重程度在不同的受影响人群中也不尽相同。大量研究表明，空气污染是导致神经退行性疾病发病率上升的重要因素。队列研究提供了令人信服的证据，证明长期暴露于不同的空气有毒物质与认知能力下降、行为障碍、记忆损伤和整体神经元健康恶化之间存在关联。此外，分子研究还发现，空气污染物会破坏人体的保护机制，参与神经炎症途径，并导致神经元表观遗传学改变。线粒体表观基因组对科学界尤为重要，因为它有可能极大地影响我们对神经退行性疾病发病机制及其在外周循环中释放的理解。虽然蛋白质特征已被广泛研究，但将循环表观遗传特征（如甲基化 DNA 片段、miRNA 和基因组相关因子）用作诊断工具和治疗靶点的可能性还需要进一步研究。利用循环表观遗传特征有望开发新的预后策略，创建最重要的疾病诊断点设备，确定治疗靶点，并利用多组学技术和人工智能开发基于临床数据的疾病模型，最终减轻神经退行性疾病的威胁和流行。

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引用次数: 0

Sex-dependent effects of short-term ethanol, energy drinks and acute noise exposure on hippocampal oxidative balance and glutamate transporter EAAT-1 during rat adolescence 短期乙醇、能量饮料和急性噪音暴露对大鼠青春期海马氧化平衡和谷氨酸转运体 EAAT-1 的影响具有性别依赖性

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-10-02 DOI: 10.1016/j.neuro.2024.10.001

Sonia Jazmín Molina , Gonzalo Nahuel Corsi , Lara Candela Araujo Añon , Laura Ruth Guelman

It is known that human adolescents often consume ethanol (EtOH) alone or mixed with energy drinks (ED), especially in noisy environments. Although these agents impact the developing brain, their effects after brief exposure or when presented together remain unclear. Given that few animal studies in this subject are available, this research aimed to study the effects of a brief exposure to these stimuli on the oxidative state and EAAT-1 glutamate transporter levels in the developing rat hippocampus (HC). Adolescent Wistar rats were subjected to a two-bottle choice, limited access to drinking in the dark paradigm, for EtOH and EtOH+ED intake, for 4 days, and subsequent acute noise exposure. Next, hippocampal catalase activity, reactive oxygen species (ROS), glutaredoxin-1 (Grx-1) and glutamate transporter EAAT-1 levels were assessed. Results showed sex-dependent alterations after exposure to these stimuli: Females consuming EtOH had higher hippocampal ROS levels, which decreased when combined with noise; males showed reduced ROS levels only after noise exposure. No significant changes occurred in catalase activity, Grx-1, or EAAT-1 levels with EtOH and noise exposure in neither sex. Additionally, ED raised EtOH consumption in both sexes, normalizing ROS levels only in females when combined with EtOH. Finally, ED consumption altered Grx-1 and EAAT-1 levels in both sexes. In summary, brief exposure to these stimuli induced sex-dependent alterations, suggesting differentiated coping strategies between sexes. Whereas ED consumption may have antioxidant effects in some cases, it could also increase excitotoxicity risk. These novel findings raise questions for future research on the underlying corresponding mechanisms.

众所周知，人类青少年经常单独饮用乙醇（EtOH）或与能量饮料（ED）混合饮用，尤其是在嘈杂的环境中。虽然这些物质会对发育中的大脑产生影响，但它们在短暂接触后或同时饮用时产生的影响仍不清楚。鉴于这方面的动物研究很少，本研究旨在研究短暂接触这些刺激物对发育中的大鼠海马（HC）氧化状态和 EAAT-1 谷氨酸转运体水平的影响。研究人员对青春期Wistar大鼠进行了为期4天的双瓶选择、限制在黑暗中饮用EtOH和EtOH+ED的范例实验，随后又对其进行了急性噪音暴露。然后，评估海马过氧化氢酶活性、活性氧（ROS）、谷草转氨酶-1（Grx-1）和谷氨酸转运体 EAAT-1 的水平。结果：暴露于这些刺激后，出现了与性别相关的变化：摄入乙醇的女性海马 ROS 水平较高，当与噪音结合时，ROS 水平降低；男性仅在暴露于噪音后 ROS 水平降低。过氧化氢酶活性、Grx-1或EAAT-1水平在暴露于EtOH和噪声时均无明显变化。此外，ED 提高了男女两性的乙醇消耗量，只有女性在与乙醇结合使用时才会使 ROS 水平恢复正常。最后，摄入乙醇会改变两性的 Grx-1 和 EAAT-1 水平。总之，短暂暴露于这些刺激会诱发与性别相关的改变，这表明两性的应对策略有所不同。在某些情况下，服用ED可能具有抗氧化作用，但也可能增加兴奋毒性风险。这些新发现为今后相应机制的研究提出了问题。

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引用次数: 0

Saroglitazar, a PPAR α/γ agonist alleviates 3-Nitropropionic acid induced neurotoxicity in rats: Unveiling the underlying mechanisms Saroglitazar 是一种 PPAR α/γ 激动剂，能减轻 3-硝基丙酸诱导的大鼠神经毒性：揭示潜在机制

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-09-24 DOI: 10.1016/j.neuro.2024.09.004

Madhuri Suma Jakkamsetti , Aravinda Sai Kolusu , Suma Rongala , Bhanu Prakash Arakareddy , Lakshmi Prashanthi Nori , Pavan Kumar Samudrala

Saroglitazar (SGZ), a peroxisomal proliferated activated receptor α/γ agonist showed neuroprotective effects in various neurodegenerative disorders like Alzheimer’s and Parkinson’s. However, no studies were performed on Huntington’s, so the goal of the current study is to examine the effect of SGZ on Huntington’s disease like symptoms induced by 3-Nitropropionic acid. In this protocol, twenty-four rats were divided into four groups, each group consisting of 6 animals. Group 1: The control group received 1 % CMC 10 mg/kg, p.o. for 14 days. Groups 2, 3, and 4 received 3-NP 15 mg/kg, i.p. from Day 1 to Day 7. Groups 3 and 4 received SGZ 5 mg/kg, p.o. and 10 mg/kg, p.o. respectively once daily from day 1 to day 14. Various behavioral tests like OFT, rotarod, hanging wire, narrow beam walk, MWM, and Y-maze were performed. On day-15, the animals were euthanised by cervical dislocation and brain sample were isolated for biochemical and histopathological analysis. Administration of 3-NP showed a significant decrease in motor coordination and cognitive function. Furthermore, 3-NP altered the activity of acetylcholinesterase, anti-oxidant enzymes, Nrf-2, NF-κB, BDNF, CREB levels, and histological features. However, treatment with SGZ showed ameliorative effects in the 3-NP induced neurotoxicity via PPAR α/γ pathway by reducing motor dysfunction, memory impairment, cholinesterase levels, oxidative stress, neuroinflammation. It also enhanced the levels of Nrf-2, BDNF, and CREB expression and improved histological features. In conclusion, treatment with Saroglitazar attenuated Huntington’s disease-like symptoms in rats which are induced by 3-NP via activation of PPAR α/γ pathway.

沙格列扎尔（SGZ）是一种过氧化物酶体增殖激活受体α/γ激动剂，在阿尔茨海默氏症和帕金森氏症等多种神经退行性疾病中显示出神经保护作用。因此，本研究的目的是检测 SGZ 对 3-硝基丙酸诱导的亨廷顿症类似症状的影响。在本方案中，24 只大鼠被分为四组，每组 6 只。第 1 组：对照组接受 1 % CMC 10 毫克/千克，口服 14 天。第 1 天至第 7 天，第 2 组、第 3 组和第 4 组接受 3-NP 15 毫克/千克，口服。第 1 天至第 14 天，第 3 组和第 4 组分别接受 SGZ 5 毫克/千克（口服）和 10 毫克/千克（口服），每天一次。进行各种行为测试，如OFT、旋转木马、悬挂钢丝、窄梁行走、MWM和Y迷宫。第 15 天，对动物实施颈椎脱臼安乐死，并分离脑样本进行生化和组织病理学分析。服用 3-NP 后，动物的运动协调能力和认知功能明显下降。此外，3-NP 还改变了乙酰胆碱酯酶的活性、抗氧化酶、Nrf-2、NF-κB、BDNF、CREB 水平和组织学特征。然而，通过 PPAR α/γ 通路，SGZ 对 3-NP 诱导的神经毒性有改善作用，可减少运动功能障碍、记忆损伤、胆碱酯酶水平、氧化应激和神经炎症。它还能提高 Nrf-2、BDNF 和 CREB 的表达水平，改善组织学特征。总之，使用沙格列扎尔治疗可减轻 3-NP 通过激活 PPAR α/γ 通路诱导的大鼠亨廷顿病样症状。

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引用次数: 0

Welding techniques and manganese concentrations in blood and brain: Results from the WELDFUMES study 焊接技术与血液和大脑中的锰浓度：WELDFUMES 研究的结果

IF 3.4 3区医学 Q2 NEUROSCIENCES

Neurotoxicology

Pub Date : 2024-09-24 DOI: 10.1016/j.neuro.2024.09.005

Per Thunberg , Gunilla Wastensson , Göran Lidén , Mary Adjeiwaah , Jens Tellman , Bernt Bergström , Louise Fornander , Peter Lundberg

This study used whole-brain mapping to investigate the effect of different welding processes on manganese (Mn) accumulation in the brain. Exposure measurements were performed at the welders’ workplaces about 3 weeks before a magnetic resonance imaging (MRI) examination. The welders were categorized into three main groups based on welding method, and the T1-relaxation rate (R1) was measured using quantitative MRI (qMRI). Welders using shielded metal arc welding (SMAW) were found to have lower accumulations of total Mn in clusters encompassing white matter, thalamus, putamen, pallidum, and substantia nigra compared with welders using inert gas tungsten arc welding (GTAW) or continuous consumable electrode arc welding (CCEAW). A positive correlation was found between Mn in red blood cells (Mn-RBC) and R1 in a region encompassing pre-and post-central gyri. The results of this study show that the accumulation of free, bound, or compartmentalized Mn ions in the brain differed depending on the welding method used. These differences were predominately located in the basal ganglia but were also found in regions encompassing white matter. The level of Mn-RBC was correlated to the deposition of Mn in the left primary somatosensory and motor cortex and may therefore be linked to neurological and neurobehavioral symptoms.

本研究采用全脑绘图法来研究不同焊接工艺对大脑中锰（Mn）积累的影响。在磁共振成像（MRI）检查前约 3 周，在焊工的工作场所进行了暴露测量。根据焊接方法将焊工分为三大组，并使用定量磁共振成像（qMRI）测量 T1 缓解率（R1）。结果发现，与使用惰性气体钨极氩弧焊（GTAW）或连续焊条电弧焊（CCEAW）的焊工相比，使用金属保护弧焊（SMAW）的焊工在白质、丘脑、丘脑、苍白球和黑质中的总锰累积量较低。研究发现，红细胞中的锰（Mn-RBC）与中央回前后区域的 R1 呈正相关。这项研究结果表明，大脑中游离的、结合的或分区的锰离子的积累因所使用的焊接方法而异。这些差异主要存在于基底节，但在包括白质的区域也有发现。Mn-RBC 的水平与左侧初级躯体感觉和运动皮层的锰沉积相关，因此可能与神经和神经行为症状有关。

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引用次数: 0