Neurotoxicology最新文献

{"title":"Developmental exposure of zebrafish to 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) elicits MPTP-like neurotoxicity.","authors":"Ji-Hang Yin, Katharine A Horzmann","doi":"10.1016/j.neuro.2025.103333","DOIUrl":"10.1016/j.neuro.2025.103333","url":null,"abstract":"<p><p>1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) is an endogenous metabolite of the industrial waste trichloroethylene (TCE) and has been implicated as a potent neurotoxicant in TCE-induced neurotoxicity. TaClo has been associated with Parkinson's disease (PD) due to its neurotoxic effects and structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Despite the similarities, limited studies have explored the comparative neurotoxicity of MPTP and TaClo within the same experimental models. Zebrafish (Danio rerio) are a powerful high throughput platform for neurotoxicology studies and have been used to evaluate TCE-associated developmental neurotoxicity; however, the role of TaClo in TCE-associated neurotoxicity in the zebrafish model is unknown. To address these gaps, we established an MPTP-induced PD zebrafish larval model and investigated the role of TaClo by comparing its neurotoxic effects with those of MPTP. We exposed embryonic zebrafish to TaClo (5, 50, or 500 ppb) or MPTP (0-17,325 ppb) for 5 consecutive days. We demonstrate that TaClo at 5 ppb elicits 303.2 ppb MPTP-like neurotoxicity in the developmental zebrafish. We determined the lethal concentration 50 of TaClo at the zebrafish larval model at 120 h post-fertilization was 7890 ppb. We show that embryonic zebrafish exposed to TaClo exhibit neurobehavioral impairments, diencephalic dopaminergic neuronal damage, increased cellular apoptosis, astrocytic loss, microgliosis, and altered glutathione peroxidase activity levels. These findings provide important insights into the neurotoxic mechanisms of TaClo and emphasize the utility of developmental zebrafish as a model for studying TaClo-induced neurotoxicity. Our work contributes to environmental contaminants research in neurodegenerative diseases by providing evidence of the potential link between TaClo exposure and PD.</p>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":" ","pages":"103333"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228288","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}

{"title":"Sevoflurane exposure in juvenile causes persistent learning and memory impairment via inducing endoplasmic reticulum stress in caenorhabditis elegans and mice","authors":"Ayang Zhao ,&nbsp;Hongjiang Jin ,&nbsp;Xiaofei Ma ,&nbsp;Guibo Fan ,&nbsp;Yueyue Gao ,&nbsp;Yuting Rong ,&nbsp;Siqi Sun ,&nbsp;Ao Zhang ,&nbsp;Sihua Qi","doi":"10.1016/j.neuro.2025.103332","DOIUrl":"10.1016/j.neuro.2025.103332","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to general anesthetics during early postnatal development is linked to enduring cognitive deficits in rodent and non-human primate models. However, the mechanisms by which inhaled anesthetics induce neuronal death and synaptic alterations remain unclear.</div></div><div><h3>Methods</h3><div><em>C. elegans</em> and neonatal male mice were administered sevoflurane. Subsequently, their learning and memory capabilities were assessed, and the potential mechanisms influencing learning and memory in <em>C. elegans</em> and mice were explored<em>.</em></div></div><div><h3>Results</h3><div>Early developmental exposure to sevoflurane resulted in learning and memory impairment in <em>C. elegans.</em> The eIF3l and ced-3 genes are critical for sevoflurane-induced developmental neurotoxicity in <em>C. elegans</em>. Endoplasmic reticulum stress is a possible mechanism underlying developmental neurotoxicity induced by sevoflurane in <em>C. elegans</em>. In neonatal mice, sevoflurane induced endoplasmic reticulum stress in hippocampal neurons independently of eIF3l, which was mitigated by TUDCA ( tauroursodeoxycholic acid, an ER stress inhibitor). Additionally, mature mice exposed to sevoflurane during the neonatal period exhibited decreased synaptic function in the hippocampus, which was alleviated by TUDCA. Persistent cognitive dysfunction was observed in adult mice exposed to sevoflurane during the neonatal period, which was alleviated by TUDCA.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that early developmental exposure to sevoflurane induces endoplasmic reticulum stress, which may result in a decrease in memory and learning capabilities. TUDCA may alleviate these effects.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103332"},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220441","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}

{"title":"Melatonin improves synaptic morphological plasticity of adolescent male rats after perinatal BDE-209 exposure via SIRT1-mediated LIMK1 and CREB signaling","authors":"Jingjing Gao ,&nbsp;Jinghua Shen ,&nbsp;Lu Gao ,&nbsp;Dongying Yan ,&nbsp;Ying Wang ,&nbsp;Jia Meng ,&nbsp;Dawei Chen ,&nbsp;Hong Li ,&nbsp;Jie Wu","doi":"10.1016/j.neuro.2025.103331","DOIUrl":"10.1016/j.neuro.2025.103331","url":null,"abstract":"<div><div>Brominated flame retardants polybrominated diphenyl ethers (PBDEs) have posed threat to ecosystems and human health, especially on neurodevelopment, while the mechanisms remain obscure. Here, we assessed recognition memory for new object and spontaneous behavior of adolescent male rats after perinatal BDE-209 exposure. Considering that the miR-34 family is linked to spines morphology and memory formation and mediates neuroprotective role of melatonin through Sirtuin1 (SIRT1), we investigated the role of miR-34 in developmental neurotoxicity of BDE-209 of rats with or without melatonin pretreatment. We analyzed dendritic arborisation and spines density of pyramidal neurons in both prefrontal cortex (PFC) and hippocampal CA1 region via Golgi-staining and Sholl tools; then conducted miRNA sequencing and verified differentially expressed miRNAs and their targets. Our findings indicated that miR-34c and miR-134 were significantly up-regulated in the hippocampus and PFC of maternal BDE-209-exposed rats, as a target of miR-34c simultaneously upstream regulator for miR-134, neuronal SIRT1 level was decreased correspondingly. Furthermore, miR-134 targeted LIMK1/cofilin and CREB/BDNF pathway contributing to changes in dendritic morphology. Melatonin pretreatment restored synaptic morphological plasticity especially spines density in hippocampal and cortical neurons, partially through elevating SIRT1 expression, and alleviated BDE-209-caused memory deficits, providing a potential neuroprotective intervention.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103331"},"PeriodicalIF":3.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206976","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}

{"title":"Tamoxifen induces partial neuroprotection against manganese toxicity in the dopaminergic REST-deleted male mice","authors":"Alexis Digman ,&nbsp;Edward Pajarillo ,&nbsp;Sanghoon Kim ,&nbsp;Itunu Ajayi ,&nbsp;Deok-Soo Son ,&nbsp;Michael Aschner ,&nbsp;Eunsook Lee","doi":"10.1016/j.neuro.2025.103330","DOIUrl":"10.1016/j.neuro.2025.103330","url":null,"abstract":"<div><div>Chronic manganese (Mn) exposure leads to manganism, a neurological disorder with Parkinson’s disease (PD)-like symptoms. Tamoxifen (TX), a selective estrogen receptor modulator (SERM), and the RE1-silencing transcription factor (REST) have both shown neuroprotective effects against Mn neurotoxicity. Since TX, via Wnt signaling, increases REST and protects dopaminergic (DAergic) neurons against Mn toxicity <em>in vitro</em>, we investigated if DAergic REST is essential for TX-induced neuroprotection, with a potential involvement of Wnt, in Mn-exposed male mice. TX pellets were implanted in wild-type (WT) and DAergic REST knockout (REST cKO) male mice prior to Mn exposure (330 μg MnCl₂, via nostril instillation) for 3 weeks, followed by behavioral and molecular analyses. The findings revealed that TX attenuated Mn-induced impairments of movement and cognition in WT mice, while those effects were diminished in REST cKO mice. The protein levels in the striatum, where DAergic nerve terminals were situated, showed that TX attenuated Mn-induced reductions in tyrosine hydroxylase and REST proteins, as well as Mn’s neurotoxicity in WT, while these protections on certain proteins were diminished in REST cKO mice. Mn impaired Wnt signaling by dysregulating Wnt3a and β-catenin proteins in WT and REST cKO mice. TX attenuated these Mn effects in WT, with less attenuation in REST cKO mice, suggesting that DAergic REST contributes to TX’s Wnt-mediated neuroprotection against Mn toxicity. These findings demonstrate that TX induces partial protection against Mn-induced toxicity and Wnt signaling disruption in the absence of DAergic REST, but DAergic REST is required for TX-induced full neuroprotection in male mice.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103330"},"PeriodicalIF":3.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186714","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}

{"title":"Association between prenatal exposures to per- and polyfluoroalkyl substances and early language development in the ECHO Cohort.","authors":"Patricia Cintora, Lesliam Quirós-Alcalá, Adaeze W Nzegwu, Sudhi Upadhyaya, Megan Woodbury, Sarah Dee Geiger, Rachel Morello-Frosch, Anne L Dunlop, Theresa M Bastain, Anne P Starling, Dana Dabelea, Carlos A Camargo, Pi-I Debby Lin, Rachel S Kelly, Assiamira Ferrara, Lisa A Croen, Thomas G O'Connor, June-Soo Park, Morgan Reynolds, Kurunthachalam Kannan, Susan L Schantz","doi":"10.1016/j.neuro.2025.103309","DOIUrl":"https://doi.org/10.1016/j.neuro.2025.103309","url":null,"abstract":"<p><strong>Background/aim: </strong>The relationship between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and child neurodevelopment remains inconclusive, and few studies have investigated associations of PFAS exposure with language development. This study drew on data from seven U.S.-based Environmental influences on Child Health Outcomes (ECHO) cohorts to investigate associations between prenatal PFAS exposures and language development in early childhood.</p><p><strong>Methods: </strong>We quantified concentrations of four PFAS in maternal plasma or serum during pregnancy. Language development was assessed using the communication scale from the Ages & Stages Questionnaires, Third Edition (ASQ®-3) in children ages 1.5-5 years (n=1503) and the NIH Toolbox Picture Vocabulary Test (PVT) in children ages 3-5 years (n=399). Associations between single PFAS and language outcomes were examined in multivariable linear and logistic regression models. PFAS mixture was examined using quantile g-computation.</p><p><strong>Results: </strong>Overall and in sex-specific analyses, we did not observe associations between individual PFAS biomarkers and language development. The PFAS mixture showed no significant associations with ASQ®-3 communication z-scores (ψ = -0.04; 95% CI: -0.86, 0.78) or PVT t-scores (ψ = 0.35; 95% CI: -1.14, 1.83). Sex-specific results showed a small but statistically significant negative association with ASQ®-3 communication scores in females (ψ = -0.46; 95% CI: -0.88, -0.05; p = 0.03) and positive, albeit not statistically significant, associations with PVT t-scores in males (ψ = 0.27; 95% CI: -1.84, 2.38) and females (ψ = 0.55; 95% CI: -1.81, 2.92).</p><p><strong>Conclusions: </strong>Prenatal concentrations of individual PFAS or their mixture were not associated with ASQ®-3 communication domain scores or PVT t-scores.</p>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":" ","pages":"103309"},"PeriodicalIF":3.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182025","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}

{"title":"Inhibitory regulation of glutamate release from rat cortical nerve terminals by thymoquinone","authors":"Mao-Hsiang Hsiao ,&nbsp;Kun‑Chieh Yeh ,&nbsp;Ming-Yi Lee ,&nbsp;Wei-Che Chiu ,&nbsp;Su-Jane Wang","doi":"10.1016/j.neuro.2025.103329","DOIUrl":"10.1016/j.neuro.2025.103329","url":null,"abstract":"<div><div>Thymoquinone (TQ), a natural compound derived from the oil of <em>Nigella sativa</em> seeds, has demonstrated neuroprotective properties. This study investigated the effects of TQ on glutamate release from rat cortical synaptosomes and explored the underlying mechanisms. TQ inhibited 4-aminopyridine (4-AP)-evoked glutamate release in a concentration-dependent manner, with an estimated IC₅₀ of 8.1 μM. This inhibitory effect was absent under Ca^2 + -free conditions and in the presence of bafilomycin A1, an inhibitor of vesicular glutamate transporter, indicating a Ca²⁺-dependent exocytotic mechanism. Consistently, TQ significantly reduced 4-AP-induced uptake of the synaptotagmin 1 luminal domain antibody (syt1-L ab), confirming suppression of synaptic vesicle exocytosis. Moreover, TQ attenuated the 4-AP-induced elevation of intraterminal Ca²⁺ without affecting synaptosomal membrane potential. Notably, the inhibitory effect of TQ on glutamate release was abolished by blockade of P/Q-type Ca²⁺ channels or inhibition of protein kinase C (PKC). Western blot analysis further revealed that TQ reduced 4-AP-induced phosphorylation of PKC, SNAP-25, and Munc18–1 in synaptosomes. Collectively, these findings suggest that TQ inhibits glutamate exocytosis from cortical synaptosomes by reducing Ca²⁺ influx through P/Q-type Ca²⁺ channels and subsequently downregulating the PKC/SNAP-25/Munc18–1 signaling cascade.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103329"},"PeriodicalIF":3.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182051","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}

{"title":"Toxicological effects of diquat on the central nervous system and associated treatment challenges","authors":"Xinyu Wang ,&nbsp;Yunxia Liu ,&nbsp;Meng Yang ,&nbsp;Yunwen Wang,&nbsp;Feng Guo,&nbsp;Lin Wang","doi":"10.1016/j.neuro.2025.103327","DOIUrl":"10.1016/j.neuro.2025.103327","url":null,"abstract":"<div><h3>Background</h3><div>Diquat is a highly toxic pyridine-based herbicide, and its central nervous system (CNS) toxicity is a major factor contributing to the high mortality rate and poor neurological outcomes in poisoned patients. Compared with other organ injuries, the complex molecular mechanisms underlying diquat-induced CNS damage and effective neuroprotective strategies remain poorly understood.</div></div><div><h3>Methods</h3><div>A systematic search and screening of relevant literature on diquat-induced CNS toxicity were conducted. Based on predefined inclusion and exclusion criteria, 21 articles were selected from 424 retrieved records, including 11 experimental and 10 case studies. A systematic review approach was employed to integrate basic research with clinical evidence.</div></div><div><h3>Results</h3><div>The study identified typical clinical manifestations of CNS damage caused by diquat poisoning (e.g., impaired consciousness, convulsions, and brainstem symptoms), along with characteristic imaging findings (e.g., lesions in the basal ganglia and brainstem). The core findings highlight six major mechanisms underlying diquat-induced neural damage: excessive activation of the oxidative stress response; pronounced neuroinflammatory cascade reactions; dysregulated autophagy function; activation of apoptotic signaling pathways; mitochondrial dysfunction; and significant alterations in the neurotransmitter system. These mechanisms are interrelated and collectively lead to neuronal death and functional impairment.</div></div><div><h3>Conclusions</h3><div>Diquat induces severe CNS damage through multiple interrelated molecular mechanisms. Current diagnostic and therapeutic strategies face significant challenges in improving neurological outcomes, particularly due to the lack of specific antidotes and targeted neuroprotective agents. Future research should aim to elucidate the underlying mechanisms in detail, explore novel neuroprotective targets, optimize comprehensive treatment protocols, and develop long-term rehabilitation strategies to reduce neurological impairment and mortality associated with diquat poisoning.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103327"},"PeriodicalIF":3.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154975","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}

{"title":"TREM2-mediated neuroinflammatory response is involved in AgNPs-induced ferroptosis in HMC3 cells","authors":"Haitao Yang,&nbsp;Menghao Guo,&nbsp;Shuyan Niu,&nbsp;Chenyu Liu,&nbsp;Tianshu Wu,&nbsp;Mengjing Cui,&nbsp;Yuying Xue","doi":"10.1016/j.neuro.2025.103326","DOIUrl":"10.1016/j.neuro.2025.103326","url":null,"abstract":"<div><div>Silver nanoparticles (AgNPs) are widely used in industrial and biomedical applications owing to their superior physicochemical properties, especially antimicrobial activity. However, their potential health risks raise concerns. Given that the central nervous system (CNS) is a major target of AgNPs, assessing their neurotoxic effects is critical for safety evaluation. Recent studies suggest that ferroptosis may play a pivotal role in AgNPs-induced neurotoxicity, yet the underlying molecular mechanisms remain unclear. This study is the first to investigate AgNPs-triggered ferroptosis in human microglial cells (HMC3) and explore the regulatory role of triggering receptor expressed on myeloid cells 2 (TREM2)-mediated inflammatory responses. Following exposure to AgNPs (0, 50, 100, and 200 μg/mL) for 48 h, HMC3 cells exhibited dose-dependent cytotoxicity. Further analyses revealed mitochondrial ultrastructural and functional damage, intracellular Fe²⁺ overload, elevated ROS levels, GSH depletion, and increased lipid peroxidation, accompanied by dysregulated expression of ferroptosis-related proteins. Inflammatory profiling demonstrated reduced TREM2 protein levels, elevated pro-inflammatory markers, and decreased anti-inflammatory markers, indicating AgNPs-induced inflammatory responses. Treatment with the TREM2 agonist COG 1410 (5 μg/mL) significantly upregulated TREM2 expression, attenuated pro-inflammatory factors, and enhanced anti-inflammatory factors. Moreover, TREM2 activation significantly inhibited AgNPs-induced ferroptosis in HMC3 cells, indicating that TREM2-mediated inflammation may play a key role in regulating this process. These findings offer new understanding of AgNPs neurotoxicity and potential therapeutic targets for reducing CNS damage from AgNPs exposure.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103326"},"PeriodicalIF":3.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149857","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}

{"title":"Hexavalent chromium neurotoxicity in Caenorhabditis elegans targeted GABAergic, cholinergic, and dopaminergic neurons, and contributed to an aged phenotype","authors":"Samuel T. Vielee ,&nbsp;Pan Chen ,&nbsp;Romina Deza-Ponzio ,&nbsp;Idoia Meaza ,&nbsp;Shreesh Raj Sammi ,&nbsp;Michael Aschner ,&nbsp;John P. Wise Jr.","doi":"10.1016/j.neuro.2025.103325","DOIUrl":"10.1016/j.neuro.2025.103325","url":null,"abstract":"<div><div>Hexavalent chromium [Cr(VI)] is a ubiquitous environmental pollutant and potent toxicant. Cr(VI) exposure impacts millions of people around the world, primarily through inhalation or ingestion. Such exposures are best known for contributing to cancers of the lung, sinus, and nasal passage, damage to kidneys and liver, and contact dermatitis. Growing evidence indicates exposure contributes to neurological conditions, but knowledge gaps persist regarding Cr(VI) neurotoxicity. Human studies report Cr(VI) contributes to autism spectrum disorders, motor neuron disease, olfactory dysfunction, and impaired memory. However, knowledge of specific targets for Cr(VI) in the brain is limited to reports of regional accumulation (greatest effects reported in the rodent hippocampus, hypothalamus, and pituitary gland), while cell-specific effects remain unknown. <em>Caenorhabditis elegans</em> is a useful high-throughput model, frequently used for metals neurotoxicity. Here, we characterize a <em>C. elegans</em> model to address knowledge gaps in Cr(VI) neurotoxicity. All Cr(VI) concentrations tested were sublethal, and we estimate bioaccumulation of Cr in worms was ∼1e10⁻⁸% of the administered dose after a 24-hour exposure. Cr(VI) initially targeted GABAergic neurons after a 6-hour exposure, while cholinergic, dopaminergic, and GABAergic neurons were affected following a 24-hour exposure. Impacts on behaviors were consistent with neurodegeneration. Further, Cr(VI) exacerbated gut autofluorescence in worms, indicative of accelerated biological aging. These data collectively address key knowledge gaps, identifying key neuronal targets and informing potential mechanisms of neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103325"},"PeriodicalIF":3.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113803","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}

{"title":"Insights into cytotoxicity and redox modulation by the herbicide linuron and its metabolite, 3,4-dichloroaniline","authors":"Md. Jakaria ,&nbsp;Jason R. Cannon","doi":"10.1016/j.neuro.2025.103324","DOIUrl":"10.1016/j.neuro.2025.103324","url":null,"abstract":"<div><div>Linuron (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) is a phenylurea herbicide used to control the growth of grasses and weeds, thereby promoting the growth of crops such as soybeans. Both linuron and its metabolite, 3,4-dichloroaniline (DCA), have been identified as having toxic effects, including reproductive and developmental toxicity. However, the potential neurotoxic effects have not been thoroughly examined. This study investigates the toxic effects of linuron and DCA in neuronal cultures. A cell viability assay was used to evaluate cytotoxicity, while an iron and arachidonic acid-induced C11-BODIPY oxidation and ABTS assay were conducted to assess the potential redox modulatory activity of the tested compounds. Our results indicated that linuron and DCA were toxic to N27 cells (rat dopaminergic neurons) at higher concentrations, particularly above 50 μM. In contrast, these compounds did not demonstrate any considerable toxicity in HT-22 cells (mouse hippocampal neurons). We also examined whether linuron and DCA influence ferroptosis, a form of regulated cell death caused by lipid peroxidation. Our findings suggest that DCA significantly interferes with the process of ferroptosis and inhibits it due to its inherent radical-trapping antioxidant (RTA) activity. In conclusion, both linuron and its metabolite DCA showed modest cytotoxicity in N27 cells, and further experiments are needed to determine whether these agents cause neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103324"},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091924","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}