Neurotoxicology最新文献

{"title":"Elevated fecal silver, lithium, and platinum in cognitive impairment: A pilot exploration of microbiota–metal interactions","authors":"David Mateo ,&nbsp;Marília Cristina Oliveira Souza ,&nbsp;Nerea Carrión ,&nbsp;Luis Heredia ,&nbsp;Cristian Cabrera ,&nbsp;Montse Marquès ,&nbsp;Eva Forcadell-Ferreres ,&nbsp;Maria Pino ,&nbsp;Josep Zaragoza ,&nbsp;José Luis Domingo ,&nbsp;Fernando Barbosa ,&nbsp;Margarita Torrente","doi":"10.1016/j.neuro.2026.103390","DOIUrl":"10.1016/j.neuro.2026.103390","url":null,"abstract":"<div><h3>Background</h3><div>Gut microbiota (GMB) and metal exposure have both been implicated in cognitive impairment (CI), including amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). However, studies integrating these areas remain scarce.</div></div><div><h3>Objective</h3><div>This pilot study aimed to investigate whether exposure to metals modulates the relationship between GMB composition and clinical outcomes in individuals with CI.</div></div><div><h3>Methods</h3><div>Stool samples were collected from aMCI (n = 12), AD (n = 18), and cognitively healthy controls (HC, n = 30). Participants were categorized into CI (n = 30) and HC (n = 30). Gut microbial diversity was assessed using shotgun sequencing, and 25 metals were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive, neuropsychological, neuropsychiatric, and functional assessments were also conducted.</div></div><div><h3>Results</h3><div>No significant differences were observed between groups in microbial richness, alpha-diversity (Shannon index), or beta-diversity (Bray–Curtis). Likewise, microbial diversity measures were not associated with cognitive outcomes. In contrast, aMCI and AD participants exhibited significantly higher fecal concentrations of silver (Ag), lithium (Li), and platinum (Pt) compared to HC (all p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>This multidimensional pilot study integrating microbiota profiling, metal exposure assessment, and cognitive evaluation, revealed elevated fecal excretion of Ag, Li, and Pt in participants with cognitive impairment, suggesting potential interactions between trace metals and neurodegenerative processes. While no significant differences in overall microbial diversity were observed between groups, these findings emphasize the need for larger, longitudinal investigations to elucidate the complex relationships among gut microbiota, metal homeostasis, and cognitive decline.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103390"},"PeriodicalIF":3.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958737","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":"Targeting glutamate receptors with IEM-1925: A strategy against soman-induced status epilepticus and neurodegeneration","authors":"Yuxin Lin,&nbsp;Qian Jin,&nbsp;Yuanqing Chen,&nbsp;Jingyan Wang,&nbsp;Yi Zhang,&nbsp;Manzhu Cao,&nbsp;Jingjing Shi,&nbsp;Liqin Li","doi":"10.1016/j.neuro.2026.103389","DOIUrl":"10.1016/j.neuro.2026.103389","url":null,"abstract":"<div><div>Exposure to organophosphorus nerve agents (OPNAs) like soman frequently develops status epilepticus (SE), leading to brain damage. Existing antiseizure medications (e.g., diazepam, DZP) often demonstrate insufficient efficacy. To develop more effective treatments for OPNA-induced seizures, this study evaluated the efficacy of glutamate receptor antagonists with distinct mechanisms of action in a soman-induced rat seizure model. After 5 min of subcutaneous exposure to 110 μg/kg soman, which induced SE, rats received intraperitoneal injections (10 mg/kg) of perampanel (PER), fanapanel (FNP), IEM-1925 (IEM), or DZP. The results showed that IEM significantly suppressed seizure activity and improved survival. The survival rate of the vehicle-treated control group was 31.25 %, whereas DZP, FNP, and IEM increased survival rates to 50 %, 43.75 %, and 56.25 % respectively. Electroencephalographic (EEG) recordings for 24 h indicated that both DZP and IEM controlled soman-induced SE. However, while DZP initially blocked the onset of seizures, they recurred after its transient anticonvulsant effect wore off. In contrast, IEM reduced behavioral convulsion intensity and total duration of SE. Histopathological examinations (HE, Nissl, immunohistochemistry, and immunofluorescence) showed that IEM attenuated hippocampal CA1, CA2, and DG neuronal damage. Behavioral tests (open field, novel object recognition, and Y maze) confirmed IEM outperformed DZP and the solvent-treated group in ameliorating soman-induced anxiety, cognitive dysfunction, and memory impairment. In conclusion, IEM demonstrates potent triple effects-antiseizure, neuroprotective, and cognitive improving in soman exposure model, providing a novel therapeutic strategy and candidate drug for the medical treatment of OPNAs poisoning.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103389"},"PeriodicalIF":3.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952523","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":"Larval zebrafish as a translational model for neurotoxicity screening of emerging psychoactive substances","authors":"Courtney Hillman ,&nbsp;James Kearn ,&nbsp;Maciej Trznadel ,&nbsp;Matthew J. Winter ,&nbsp;Matthew O. Parker","doi":"10.1016/j.neuro.2026.103386","DOIUrl":"10.1016/j.neuro.2026.103386","url":null,"abstract":"<div><div>The rapid emergence of novel psychoactive substances poses a growing neurotoxicological concern, characterised by poorly defined mechanisms, high potency, and escalating overdose fatalities. Effective treatments remain limited, highlighting the need for scalable <em>in vivo</em> systems capable of identifying hazardous pharmacological profiles before widespread harm occurs. Here, we evaluated larval zebrafish (<em>Danio rerio</em>) as a medium/high-throughput model for early hazard assessment of γ-aminobutyric acid (GABA)_A positive allosteric modulators (PAMs) and N-methyl-<span>D</span>-aspartate (NMDA) receptor antagonists. Behavioural analysis of 4 days post-fertilisation (dpf) larvae revealed concentration-dependent locomotor effects consistent with mammalian pharmacodynamics, while whole-body bioanalysis confirmed compound uptake, revealing substance-specific differences in internal exposure. Notably, diazepam and tiletamine deviated from expected class profiles, highlighting the model’s sensitivity to compounds with distinctive neuropharmacological signatures. These findings demonstrate the translational value of larval zebrafish for rapid neurotoxicity screening and pharmacodynamic profiling, offering an ethically advantageous, 3Rs-aligned platform to inform overdose treatment development and prioritisation of emerging psychoactive threats.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103386"},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903965","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":"Ketamine's brain spatial distribution and metabolic effects in a mouse model of anxiety: Insight into in situ mass spectrometry imaging and metabolomics methods","authors":"Hong Yang ,&nbsp;Weihao Fan ,&nbsp;Xinyu Yang ,&nbsp;Ying Wei ,&nbsp;Li Xiao ,&nbsp;Hongkun Yang ,&nbsp;Linzhi Jiang ,&nbsp;Jian Li ,&nbsp;Kaiting Shi ,&nbsp;Shuang Zhao ,&nbsp;Lin Yang ,&nbsp;Yi Ye ,&nbsp;Linchuan Liao","doi":"10.1016/j.neuro.2025.103374","DOIUrl":"10.1016/j.neuro.2025.103374","url":null,"abstract":"<div><div>Ketamine, an N-methyl-<span>D</span>-aspartate (NMDA) receptor antagonist, exhibits both therapeutic potential and abuse liability. However, the spatial distribution of ketamine across brain regions remains poorly characterized. Meanwhile, elucidating the mechanism underlying ketamine-induced psychiatric disorders through the investigation of metabolite alterations in the specific brain regions targeted by ketamine is of crucial significance. This study investigated the neurochemical effects of chronic ketamine administration in C57BL/6 mice using in situ mass spectrometry imaging (MSI) and metabolomics. Mice treated with ketamine (30 mg/kg daily for 15 days) exhibited increased anxiety-like behaviors without cognitive deficits. MSI revealed ketamine accumulation in the cerebral cortex, midbrain, and cerebellum, while the key neurotransmitter γ-aminobutyric acid (GABA) distribution shifted toward thalamic and striatum regions. The prefrontal cortex and cerebellum were selected as targeted brain regions for metabolomics analysis based on the MSI results. In metabolomics results, 73 and 134 differential metabolites in the prefrontal cortex and cerebellum were identified, respectively, predominantly linked to Alanine, aspartate, and glutamate metabolism, Estrogen signaling pathway, and GABAergic synapse pathways. This study integrated behavioral assessments, in situ MSI, and metabolomics to visually resolve and multidimensionally correlate ketamine's spatial distribution in the brain with region-specific metabolic changes in a ketamine-induced anxiety model. The findings reveal distinct neurochemical disruptions across brain regions and offer a groundwork for further elucidating the mechanisms of ketamine-related anxiety.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103374"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844049","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":"Power calculations for larval zebrafish in light-dark transition test for developmental neurotoxicity","authors":"Kathryn S. Konrad ,&nbsp;Katherine Allen-Moyer ,&nbsp;Lee Ellis ,&nbsp;Ellen Hessel ,&nbsp;Oihane Jaka ,&nbsp;Arantza Muriana ,&nbsp;Beatriz Molina Martínez ,&nbsp;Ana del Pozo ,&nbsp;Valentina Schiavone ,&nbsp;Vincenzo Di Donato ,&nbsp;Claudia Miguel Sanz ,&nbsp;Lisa Truong ,&nbsp;Robyn Tanguay ,&nbsp;Keith R. Shockley ,&nbsp;Kristen Ryan ,&nbsp;Jui-Hua Hsieh","doi":"10.1016/j.neuro.2025.103371","DOIUrl":"10.1016/j.neuro.2025.103371","url":null,"abstract":"<div><div>The link between environmental chemical exposures and neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder underscores the need to develop efficient developmental neurotoxicity (DNT) assays for chemical evaluation. The zebrafish Light-Dark Transition Test (LDTT) assesses changes in zebrafish larval behavioral responses to chemical exposure by recording their distance moved under alternating light and dark conditions. To gain confidence in classifying a chemical as having a DNT effect for the LDTT assay, it is important to determine the minimum sample size to obtain a robust behavioral response. We calculated statistical power under common models based on LDTT data collected from four laboratories using standard protocol parameters, where each 96-well plate contained 5–7 test concentrations and 12–16 vehicle control wells (1 larva/well). Power calculations were conducted to identify concentration effects using t-tests, analysis of variance (ANOVA), and repeated measures ANOVA (RMANOVA), with data from four endpoints: Total Distance, Movement Similarity, Distance Change, and Distance Shift. The tests showed the highest power for the Movement Similarity and Distance Change endpoints, which had the lowest intra- and inter-laboratory variability, resulting in a smaller necessary sample size to estimate dose effects. The use of these endpoints more than doubled the power of the statistical tests for the Total Distance endpoints using the same sample size and typically required between 8 and 32 samples to achieve 80 % power at a 20 % effect size. This work demonstrates that the LDTT can be improved for detecting DNT effects by careful consideration of endpoint selection, data transformation, and type of statistical test.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103371"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834322","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":"Methylene blue protects oligodendroglial cell models of multiple systems atrophy against hydrogen peroxide-mediated oxidative stress","authors":"Kayla M. Elias,&nbsp;William F. Muliawan,&nbsp;Muriel J. Moon,&nbsp;Gunnar F. Kwakye","doi":"10.1016/j.neuro.2025.103366","DOIUrl":"10.1016/j.neuro.2025.103366","url":null,"abstract":"<div><div>Multiple Systems Atrophy (MSA) is a rare, neurodegenerative disorder associated with impaired alpha (α)-synuclein (α-syn) protein function. α-syn can aggregate within oligodendrocytes, activating oxidative stress pathways and ultimately leading to cell death. Point mutations in the α-syn gene (<em>SNCA</em>) are associated with MSA–A53E and G51D, but cases are mainly idiopathic. Methylene Blue (MB) is an organic dye that has been demonstrated to attenuate oxidative stress in cell models of Parkinson’s and Huntington’s disease. We hypothesized that MB would protect α-syn stably transfected oligodendroglial cell models of MSA against hydrogen peroxide (H₂O₂)-induced cellular stress. We used four α-syn stably transfected OLN-93 rat oligodendroglial cell lines expressing either an empty plasmid (EP), overexpressed humanized wild-type α-syn (WT-α-syn), or humanized α-syn with either point mutation (A53E-α-syn, G51D-α-syn). Upon 3 h (h) pre-treatment of OLN-93 cells with MB, followed by 1 h or 3 h exposure to H₂O₂, we report that MB does not enact toxic effects but rather substantially improves cell viability and metabolic capability and lowers H₂O₂-induced cell death in the OLN-93 MSA cell models. MB also significantly reduced H₂O₂-induced early (1 h) ROS production in the cytosol and mitochondria and the expression of oxidative stress and modified antioxidant-related proteins, including Nuclear factor erythroid 2-related factor 2 (NRF2), affiliated Kelch-like ECH-associated protein 1 (KEAP1), Heme Oxygenase 1 (HO1), and Adenosine Monophosphate-Activated Protein Kinase (AMPK) after 3 h exposure. Our current data suggest a novel glioprotective role for MB in MSA pathology, specifically against H₂O₂-mediated oxidative injury, and invite future work to investigate MB glioprotection in other <em>in vivo</em> MSA models.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103366"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781557","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":"Cadmium exposure at low environmental levels induces cognitive decline in aged male mice","authors":"Gahyun Lim ,&nbsp;Ho Young Lee ,&nbsp;Zachery R. Jarrell ,&nbsp;Seong Su Kang ,&nbsp;Dean P. Jones ,&nbsp;Young-Mi Go","doi":"10.1016/j.neuro.2025.103376","DOIUrl":"10.1016/j.neuro.2025.103376","url":null,"abstract":"<div><div>Cadmium (Cd) is a neurotoxic metal that accumulates via dietary, environmental, and occupational sources and is closely linked to oxidative stress and neuroinflammation. Little is known about the mechanistic effects of low-dose environmental Cd as found in the human diet on cognition in aged mice. Male aged mice (C57BL/6 J, 20 months old) received water with or without 3.3 mg/L Cd for 12 weeks. Cognitive function was assessed using the Y-maze, thiol/disulfide redox states were analyzed by high-performance liquid chromatography, brain Cd levels were determined by inductively coupled plasma mass spectrometry, hippocampal morphology was examined by histological analysis, and metabolomics was analyzed by high-resolution mass spectrometry. Low-dose environmental Cd exposure led to brain Cd accumulation and impaired cognitive function in aged male mice, accompanied by reduced hippocampal neuronal density in the cornu ammonis 1 region. Cd shifted the plasma redox toward a more oxidizing state, along with elevated hydroxytetradecanoic acid and decreased N-oleoylethanolamine in the brain. Cd decreased bioactive signaling lipids (lysophosphatidic acid, oleamide, sphingomyelin, sphingosine) and selectively acylcarnitine levels in the brain. Increased pyridoxal phosphate and lipoamide and decreased glutamine brain levels suggest potential compensatory responses. Exposure to low environmental levels of Cd in aged male mice disrupts redox homeostasis and systemic lipid metabolism, leading to cognitive decline, accompanied by compensatory responses. The results suggest that environmental Cd at levels found in the human diet could contribute to cognitive decline.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103376"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857364","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 effects of (synthetic) cannabinoids and (designer) benzodiazepines on spontaneously active neuronal networks of primary rat cortical cultures in vitro","authors":"J. Pepijn Wopken ,&nbsp;Jack R. Thornton ,&nbsp;Regina G.D.M. van Kleef ,&nbsp;Remco H.S. Westerink","doi":"10.1016/j.neuro.2025.103379","DOIUrl":"10.1016/j.neuro.2025.103379","url":null,"abstract":"<div><div>The use of novel psychoactive substances (NPS) has been increasing over the last 20 years. Given the coinciding increasing number of health incidents, it is of paramount importance to comprehend the neurotoxic hazards associated with these often potent but poorly characterized designer drugs. The objective of this study was therefore to investigate the neuromodulatory effects of various (designer) drugs, including cannabidiol (CBD), a synthetic cannabinoid receptor agonist (RCS-4), three canonical benzodiazepines (diazepam, oxazepam, and lorazepam) and two designer benzodiazepines (flunitrazolam and fluetizolam). To that aim, we measured changes in spontaneous neuronal activity following acute drug exposure in primary rat cortical cultures grown on microelectrode arrays (MEAs). Acute exposure to ≥ 3 µM CBD resulted in a concentration-dependent decrease of all major activity parameters, such as the number of spikes, the number of bursts, the number of spikes in a burst, burst duration, the number of network bursts, the number of spikes in a network burst, and network burst duration. These effects were comparable to those observed following acute exposure to the synthetic cannabinoid receptor agonist RCS-4, which inhibited neuronal activity at ≥ 1 µM. At the highest concentration, the decrease in neuronal activity was paralleled by an increase in burst duration. The three canonical benzodiazepines (diazepam, oxazepam, and lorazepam) concentration-dependently decreased neuronal activity (number of spikes, number of bursts and number of network bursts) with lowest observed effect concentrations (LOECs) of 0.1 µM, 1 µM and 0.1 µM, respectively. The decrease in neuronal activity was paralleled by an increase in burst duration, which was particularly profound for diazepam. The two designer benzodiazepines (flunitrazolam, and fluetizolam) potently decreased neuronal activity with LOECs of 0.01 µM and 0.03 µM, respectively. Comparable to the canonical benzodiazepines, the decrease in neuronal activity was paralleled by a marked increase in burst duration. Our findings demonstrate the applicability of MEA recordings for neurotoxicity assessment and potency ranking of diverse (designer) drugs. The strong potency of some of these drugs is particularly concerning and underscores the urgent need for better regulation and control of these substances to safeguard public health.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"112 ","pages":"Article 103379"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885306","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":"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}