Neurotoxicology最新文献

{"title":"Interactive effect of children’s copper exposure and socioeconomic status on preschoolers’ cognitive development","authors":"Hualong Zhen ,&nbsp;Linlin Zhu ,&nbsp;Xuemei Hao ,&nbsp;Jingru Lu ,&nbsp;Yufan Guo ,&nbsp;Chunmei Liang ,&nbsp;Juan Tong ,&nbsp;Fangbiao Tao ,&nbsp;Jiong Li ,&nbsp;Kun Huang","doi":"10.1016/j.neuro.2025.103377","DOIUrl":"10.1016/j.neuro.2025.103377","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore the interaction effects of children's plasma copper (Cu) levels and socioeconomic status (SES) on cognitive function in preschoolers.</div></div><div><h3>Methods</h3><div>This study utilized follow-up data from the China National Birth Cohort conducted at Ma’anshan Maternal and Child Health Center between May 2017 and September 2018. Cognitive development in 3-year-old children was assessed by trained professionals using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Plasma Cu concentrations were measured by inductively coupled plasma mass spectrometry. Family SES was assessed as a composite index derived from a baseline parental questionnaire. Restricted cubic spline plots and Poisson regression models were applied respectively to analyze the independent and interactive effects of children’s Cu exposure and SES on preschoolers’ cognitive development.</div></div><div><h3>Results</h3><div>The median plasma Cu concentration was 1062.8 µg/L (IQR: 931.9–1229.3 µg/L). Compared to high SES, low SES was associated with an increased risk of abnormalities in cognitive function (OR=2.56, 95 % CI: 1.27–5.14), receptive communication (OR=2.87, 95 % CI: 1.22–6.80), expressive communication (OR=1.77, 95 % CI: 1.23–2.54), and fine motor (OR=2.57, 95 % CI: 1.19–5.56). A medium or high concentration of Cu was associated with an increased risk of abnormalities in cognition and expressive communication compared to a low concentration of Cu. Children with medium Cu level and low SES had an increased risk of abnormalities in cognition (OR=9.88, 95 % CI: 1.26–77.47) and expressive communication (OR=2.85, 95 % CI: 1.33–6.10) compared to low Cu/high SES. Similarly, the combination of high Cu level and low SES was associated with an increased risk of abnormalities in cognition (OR=14.35, 95 % CI: 1.81–113.52) and expressive communication (OR=3.87, 95 % CI: 1.84–8.17).</div></div><div><h3>Conclusions</h3><div>Our findings revealed that low SES and children’s high concentrations of Cu were associated with preschoolers’ cognitive development both independently and interactively.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103377"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885307","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 late-life air pollution exposure and medial temporal lobe atrophy in older women","authors":"Xinhui Wang ,&nbsp;Lauren E. Salminen ,&nbsp;Andrew J. Petkus ,&nbsp;Ira Frahmand ,&nbsp;Joshua Millstein ,&nbsp;Daniel P. Beavers ,&nbsp;Mark A. Espeland ,&nbsp;Guray Erus ,&nbsp;Meredith N. Braskie ,&nbsp;Paul M. Thompson ,&nbsp;Margaret Gatz ,&nbsp;Helena C. Chui ,&nbsp;Susan M. Resnick ,&nbsp;Joel D. Kaufman ,&nbsp;Stephen R. Rapp ,&nbsp;Sally Shumaker ,&nbsp;Mark Brown ,&nbsp;Diana Younan ,&nbsp;Jiu-Chiuan Chen","doi":"10.1016/j.neuro.2025.103378","DOIUrl":"10.1016/j.neuro.2025.103378","url":null,"abstract":"<div><div>Ambient air pollution exposures increase risk for Alzheimer’s disease (AD) and related dementias, possibly due to structural changes in the medial temporal lobe (MTL). However, previous MRI studies examining exposure effects on the MTL were cross-sectional and mostly focused on the hippocampus, yielding mixed results. We addressed these limitations using longitudinal data collected from 653 cognitively unimpaired community-dwelling women from the Women’s Health Initiative Memory Study with two MRI scans (M_age at MRI-1 =77.3 ± 3.5years). We used linear regressions to examine relationships between 3-year annual average exposures to fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) prior to MRI-1, and 5-year volume changes in the bilateral hippocampus, amygdala, parahippocampal gyrus (PHG), and entorhinal cortex (ERC), which were summed to operationalize MTL volume. Covariates included intracranial volume, sociodemographic, lifestyle, and clinical characteristics. For each interquartile increase of PM_2.5 (3.26 µg/m³) and NO₂ (6.77 ppb), adjusted MTL volume had greater shrinkage by 0.32 cm³ (95 %CI=[-0.43,-0.21]) and 0.12 cm³ (95 %CI=[-0.22,-0.01]), respectively. Exposure effects did not differ by <em>APOE</em> ε4 genotype, sociodemographic, or cardiovascular risk factors. Subregionally, higher PM_2.5 was associated with greater PHG and ERC atrophy, and higher NO₂ was associated with greater PHG atrophy. Brain associations with PM_2.5 were not significant among women residing in locations that met air quality standards (PM_2.5&lt;9 µg/m³). Collectively, late-life PM_2.5 and NO₂ exposures were associated with greater MTL atrophy in cognitively unimpaired older women, especially in the PHG and ERC. These cortical MTL subregions are among the earliest affected by AD neuropathology – and may be preferentially vulnerable to air pollution neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103378"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885308","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":"Zebra_K+ : High-throughput analysis of acoustic startle response plasticity in zebrafish embryos and larvae in neurotoxicity testing","authors":"Niki Tagkalidou ,&nbsp;Ouwais Aljabasini ,&nbsp;Sergi Pujol ,&nbsp;Eva Prats ,&nbsp;Josep Maria Porta ,&nbsp;Carlos Barata ,&nbsp;Demetrio Raldúa","doi":"10.1016/j.neuro.2025.103372","DOIUrl":"10.1016/j.neuro.2025.103372","url":null,"abstract":"<div><div>The acoustic startle response (ASR) is a conserved sensorimotor reflex widely used to investigate neural plasticity, sensorimotor gating, and neurotoxicity. While zebrafish is an established vertebrate model for ASR analysis, most existing platforms were originally optimized for 6 dpf larvae, which constrains applications requiring reliable assessment of earlier developmental stages. Here, we introduce Zebra_K⁺, a modular extension of the previously developed Zebra_K platform, designed for high-throughput kinematic analysis of ASR in zebrafish embryos (5 days post-fertilization, dpf) and early larvae (6–7 dpf). The system enables simultaneous quantification of ASR kinematics, sensitivity, short-term habituation, and prepulse inhibition (PPI) in up to 25 individuals. Using the NMDA receptor antagonist ketamine, the dopamine receptor agonist apomorphine, and the D₂ receptor antagonist haloperidol, we validated the platform’s ability to detect pharmacologically induced and developmentally specific alterations in startle plasticity. Ketamine reduced habituation and PPI at all developmental stages, whereas apomorphine selectively impaired PPI, an effect that was reversed by haloperidol only at 7 dpf. These results demonstrate the neurodevelopmental progression of glutamatergic and dopaminergic modulation of sensorimotor gating and establish Zebra_K⁺ as a modular technological platform that supports the development of New Approach Methods (NAMs) for neurotoxicological screening and developmental neuropharmacology.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103372"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834368","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":"A hyperpolarization-activated cyclic nucleotide-gated channel inhibitor mitigates brain mitochondrial oxidative stress, but does not affect other neuropathological","authors":"Hiranya Pintana ,&nbsp;Nattayaporn Apaijai ,&nbsp;Adivitch Sripusanapan ,&nbsp;Titikorn Chunchai ,&nbsp;Damrongsak Jinarat ,&nbsp;Aphisek Kongkaew ,&nbsp;Nipon Chattipakorn ,&nbsp;Siriporn C. Chattipakorn","doi":"10.1016/j.neuro.2025.103341","DOIUrl":"10.1016/j.neuro.2025.103341","url":null,"abstract":"<div><h3>Background</h3><div>The effects of ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel blocker, on doxorubicin-induced chemobrain remain unclear. This study aimed to investigate whether ivabradine mitigates doxorubicin-induced chemobrain by improving cognitive function, hippocampal synaptic plasticity, and mitochondrial function, while reducing oxidative stress, inflammation, and blood-brain barrier (BBB) disruption in male rats.</div></div><div><h3>Methods</h3><div>Twenty-four male rats were randomly assigned to one of four groups: control-vehicle treated, control-ivabradine treated, doxorubicin-vehicle treated, and doxorubicin-ivabradine treated. Control-rats received normal saline, while doxorubicin-treated rats were given doxorubicin (3 mg/kg/day) intraperitoneally on days 0, 4, 8, 15, 22, and 29. Ivabradine (10 mg/kg) was given orally from day 0 to day 29. On day 30, cognitive function was evaluated using the novel object location (NOL) test. Following euthanasia, hippocampal synaptic plasticity, mitochondrial function, BBB integrity, brain oxidative stress and inflammation were assessed.</div></div><div><h3>Results</h3><div>Doxorubicin treatment led to impaired performance in the NOL test, reduced hippocampal synaptic plasticity, disruption of mitochondrial function and BBB integrity, alongside increased oxidative stress and inflammation in the brain. Ivabradine reduced the level of mitochondrial reactive oxygen species (ROS), but did not significantly improve NOL performance or synaptic plasticity in doxorubicin-treated rats. However, ivabradine partially restored hippocampal dendritic spine morphology and reduced oxidative stress and inflammation in the brain.</div></div><div><h3>Conclusion</h3><div>Doxorubicin-induced chemobrain resulted in cognitive impairment and brain pathologies. Ivabradine reduced mitochondrial ROS and alleviated oxidative stress and inflammation in the brain, but did not improve cognitive function or synaptic plasticity. Higher doses of ivabradine may be required for more effective neuroprotection in chemobrain.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103341"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409687","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":"The role of ER/ERK/CREB pathway mediated mitophagy in bisphenol F-induced cognitive function changes in young female rats","authors":"Wenhe Wang,&nbsp;Zeqin Peng,&nbsp;Xinyi Feng,&nbsp;Zixuan Chen,&nbsp;Jie Zhang,&nbsp;Tianwenjing Huang,&nbsp;Qin Zhang,&nbsp;Dan Wu,&nbsp;Qin Liu","doi":"10.1016/j.neuro.2025.103340","DOIUrl":"10.1016/j.neuro.2025.103340","url":null,"abstract":"<div><div>Bisphenol F (BPF) is a widespread industrial chemical and suspected neurotoxicant, yet its effects on cognitive function and the underlying mechanisms remain unclear. This study aimed to investigate whether BPF exposure induced cognitive function changes in young female rats were associated with ER/ERK/CREB pathway and subsequent mitophagy. 4-week-old Sprague-Dawley female rats received BPF via oral gavage (25 or 250 μg/kg bw/d) for 4 weeks. Cognitive function was evaluated using the Morris water maze and novel object recognition test during the last week of exposure. Hippocampal tissue was analysed for histomorphology, ER/ERK/CREB pathway changes, mitophagy and apoptosis. In this study, spatial learning in rats was transiently impaired, whereas long-term spatial memory remained unchanged in rats following BPF exposure. The recognition capability was improved as the dose increased. At the molecular level, the protein related to ER/ERK/CREB pathway, mitophagy and apoptosis were downregulated. Moreover, the mitophagy was downregulated in hippocampal CA1 region. These findings suggested that BPF exposure affected cognitive functions in young female rats, which was associated with the alterations of mitophagy mediated by ER/ERK/CREB pathway.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103340"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409707","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":"DDT exposure induces microglial activation and disease-associated microglial signatures: Relevance to mechanisms of Alzheimer’s disease","authors":"Isha Mhatre-Winters ,&nbsp;Aseel Eid ,&nbsp;Nicole Blum ,&nbsp;Yoonhee Han ,&nbsp;Ferass M. Sammoura ,&nbsp;Long-Jun Wu ,&nbsp;Jason R. Richardson","doi":"10.1016/j.neuro.2025.103343","DOIUrl":"10.1016/j.neuro.2025.103343","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models.</div></div><div><h3>Objective</h3><div>Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice.</div></div><div><h3>Methods</h3><div>DDT-induced inflammatory and disease-associated microglial (DAM) gene expression were determined in PMG by qPCR and immunocytochemistry, with and without pretreatment with the sodium channel antagonist tetrodotoxin (TTX). Furthermore, 4–5-month-old C57BL/6J mice received a single oral dose of 30 mg/kg DDT for 24 h, and the hippocampal and frontal cortical expression of proinflammatory and DAM genes was measured.</div></div><div><h3>Results</h3><div>PMG exposed to DDT (0.5–5.0 µM) elicited a concentration-dependent upregulation in <em>Il-1b, Il-6, Nos2,</em> and <em>Tnfa</em> mRNA levels. These effects were blocked by TTX, demonstrating the role of DDT-microglial sodium channel interactions in mediating this response. C57BL/6J mice exposed to DDT demonstrated significantly increased <em>Nos2</em>, <em>Il-1b</em>, and <em>Il-6</em> mRNA in the frontal cortex (1.5–2.3-fold), and <em>Nos2</em>, <em>Il-1b,</em> and <em>Tnfa</em> (1.5–1.8-fold) in the hippocampus. Furthermore, microglial homeostatic genes were downregulated, while stage-1 DAM genes were upregulated both <em>in vitro</em> and <em>in vivo</em>. Notably, <em>Apoe</em> and <em>Trem2</em> were only upregulated in the females.</div></div><div><h3>Conclusion</h3><div>These data indicate that DDT increases neuroinflammation, which may result from direct actions of DDT on microglia, providing a novel pathway by which DDT may contribute to AD risk.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103343"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445676","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 ,&nbsp;Lesliam Quirós-Alcalá ,&nbsp;Adaeze W. Nzegwu ,&nbsp;Sudhi Upadhyaya ,&nbsp;Megan Woodbury ,&nbsp;Sarah Dee Geiger ,&nbsp;Rachel Morello-Frosch ,&nbsp;Anne L. Dunlop ,&nbsp;Theresa M. Bastain ,&nbsp;Anne P. Starling ,&nbsp;Dana Dabelea ,&nbsp;Carlos A. Camargo Jr. ,&nbsp;Pi-I Debby Lin ,&nbsp;Rachel S. Kelly ,&nbsp;Assiamira Ferrara ,&nbsp;Lisa A. Croen ,&nbsp;Thomas G. O’Connor ,&nbsp;June-Soo Park ,&nbsp;Morgan Reynolds ,&nbsp;Kurunthachalam Kannan ,&nbsp;Susan L. Schantz","doi":"10.1016/j.neuro.2025.103309","DOIUrl":"10.1016/j.neuro.2025.103309","url":null,"abstract":"<div><h3>Background/Aim</h3><div>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.</div></div><div><h3>Methods</h3><div>We quantified concentrations of four PFAS in maternal plasma or serum during pregnancy. Language development was assessed using the communication scale from the Ages &amp; 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 individual PFAS and language outcomes were examined in multivariable linear and logistic regression models. PFAS mixture was examined using quantile g-computation.</div></div><div><h3>Results</h3><div>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).</div></div><div><h3>Conclusions</h3><div>Prenatal concentrations of individual PFAS or their mixture were not associated with ASQ®-3 communication domain scores or PVT t-scores.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103309"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","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":"Chronic cisplatin treatment in young mice induces long-term complications in the peripheral nervous system in a sex-dependent manner","authors":"Laura Yanneth Ramírez-Quintanilla,&nbsp;Santos Adrián Pérez-Reyes,&nbsp;Martin de Jesus Salazar-Hernández,&nbsp;Héctor Fabián Torres-Rodríguez,&nbsp;Virginia Margarita Vargas-Muñoz,&nbsp;Ana Rebeca García-Araujo,&nbsp;Rosa Issel Acosta-González,&nbsp;Enriqueta Muñoz-Islas,&nbsp;Juan Miguel Jiménez-Andrade","doi":"10.1016/j.neuro.2025.103318","DOIUrl":"10.1016/j.neuro.2025.103318","url":null,"abstract":"<div><div>Cisplatin-induced peripheral neuropathy (CIPN) is one of the most prevalent long-term complications in pediatric cancer survivors reaching adulthood. However, very few studies have evaluated the long-term effects of cisplatin administered to the young population on the peripheral nervous system and assessed whether these effects are sex-dependent. Thus, we aimed to assess baseline mechanical withdrawal thresholds (a CIPN measurement), the density of CGRP⁺ and PGP9.5⁺ axons in the glabrous skin, changes in different markers in DRG, and determine pain-like responses after intra-plantar capsaicin in female and male mice at 4 weeks after cessation of cisplatin. Four-week-old BALB/c mice were treated with cisplatin (4 mg/kg, intraperitoneally, twice weekly for 4 weeks). Four weeks after cessation of cisplatin, these mice, at 12 weeks of age, exhibited significant hindpaw mechanical hypersensitivity, which was greater in magnitude in female mice compared to male mice. At 13 weeks old, cisplatin-treated mice also had a greater density of CGRP⁺ and PGP9.5⁺ intraepidermal nerve fibers compared to saline-treated groups in female and male mice, independent of sex. The number of CGRP⁺ and ATF3⁺ neuronal profiles and CD68⁺ monocyte/macrophage in L4 DRG was higher in cisplatin-treated mice than in saline-treated mice, independent of sex. Intra-plantar capsaicin injection in adult mice resulted in greater and longer flinching and guarding behaviors in cisplatin-pretreated mice compared to saline-pretreated mice. The enhanced capsaicin-induced pain behaviors were significantly greater in female compared to male mice. These findings demonstrate long-term, partially sex-related complications in the peripheral nervous system following cisplatin treatment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103318"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033708","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":"Long-term occupational exhaust fumes exposure and delayed cognitive impairment in older adults: A cross-sectional study in U.S","authors":"Lili Liang ,&nbsp;Perry E. Sheffield ,&nbsp;Rose Saint Fleur-Calixte ,&nbsp;Tianxu Xia ,&nbsp;Spencer Xinyi Zhang ,&nbsp;Jenny J. Lin","doi":"10.1016/j.neuro.2025.103336","DOIUrl":"10.1016/j.neuro.2025.103336","url":null,"abstract":"<div><h3>Background</h3><div>Occupational exposure to exhaust fumes, containing neurotoxic particulate matter and polycyclic aromatic hydrocarbons (PAHs), is associated with cardiopulmonary diseases, but its cognitive effects in aging workers remain insufficiently studied. Given increasing occupational longevity, understanding these risks is critical for dementia prevention.</div></div><div><h3>Methods</h3><div>We analyzed data from 1110 adults aged 60 years and older in the 2011–2012 National Health and Nutrition Examination Survey (NHANES), comparing cognitive performance between exposed (24 %) and unexposed groups. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer’s Disease Word List Learning Test (CERAD-WL), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Distributed lag nonlinear models (DLNMs) evaluated non-linear and time-lagged effects of exposure duration.</div></div><div><h3>Results</h3><div>Exposed workers were predominantly male (81.6 % vs. 41.8 %), had lower educational attainment (31.2 % vs. 24.4 % with less than high school education), and exhibited higher rates of smoking (65.0 % vs. 48.6 %) and excessive alcohol use (15.7 % vs. 7.0 %). Occupational exposure was associated with significant cognitive impairments in delayed memory (odds ratio [OR] = 2.55, 95 % confidence interval [CI]: 1.61–4.05), verbal fluency (OR 2.41, 1.48–3.94), and processing speed (OR 1.95, 1.19–3.18). The DLNM analyses revealed a biphasic response: minimal effects at &lt; 20 years of exposure, but major declines after 30 years, with a 15–25-year latency period.</div></div><div><h3>Conclusion</h3><div>Prolonged occupational exhaust fume exposure is associated with domain-specific cognitive decline, particularly affecting memory and executive function. The dose-response relationship underscores cumulative neurotoxicity, emphasizing the need for targeted protections for high-exposure workers.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103336"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337259","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":"Age-dependent effects of hyperhomocysteinemia on neural differentiation and retinal development","authors":"Manuela Sozo Cecchini,&nbsp;Madson Silveira de Melo ,&nbsp;Evelise Maria Nazari","doi":"10.1016/j.neuro.2025.103339","DOIUrl":"10.1016/j.neuro.2025.103339","url":null,"abstract":"<div><div>Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine levels, is linked to developmental abnormalities, yet its impact on early eye development remains poorly understood. Given the well-documented neurotoxic effects of HHcy on central nervous system (CNS) development, this study aimed to investigate the age-specific effects of HHcy on eye development, focusing on retinal morphology, ultrastructure, vascular integrity, DNA integrity, apoptosis, and neural survival and differentiation. Fertilized <em>Gallus domesticus</em> embryos received 20 μmol homocysteine at embryonic day 2 (E2) and were analyzed at E6 and E10, key stages of eye organization and retinal layering. Although HHcy exposure did not alter retinal thickness, ultrastructural abnormalities indicating subcellular stress, such as dilated perinuclear space and rough endoplasmic reticulum cisternae, were observed. Disruptions on vascular integrity, induced by HHcy exposure were evident at both ages. DNA damage and upregulation of cell cycle regulators were noted at E6 but normalized by E10. Despite this, a reduction in cell proliferation was observed at both ages. Apoptosis increased at E10, suggesting heightened cell death during later retinal development. Neural differentiation and expression of neurotrophic factors were also impaired. Although overall retinal morphology appeared intact, HHcy induced significant molecular and structural disruptions, indicating a multifactorial, temporally dynamic mechanism of toxicity. These findings highlight the sensitivity of developing eye tissues to metabolic imbalance and suggest that even transient elevations in HHcy can interfere with critical developmental processes. This study underscores the potential role of HHcy in eye congenital anomalies and emphasizes the importance of maintaining homocysteine homeostasis during early embryogenesis.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103339"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355447","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}