Neurotoxicology最新文献

{"title":"Microglia as a key mediator in rosuvastatin-associated cognitive impairment","authors":"Xianzheng Sang ,&nbsp;Yichao Ye ,&nbsp;Chengzi Yang ,&nbsp;Xiaoxiang Hou ,&nbsp;Yangu Guo ,&nbsp;Hantong Shi ,&nbsp;Chunhui Wang ,&nbsp;Wen Chen ,&nbsp;Danfeng Zhang ,&nbsp;Lijun Hou","doi":"10.1016/j.neuro.2026.103405","DOIUrl":"10.1016/j.neuro.2026.103405","url":null,"abstract":"<div><h3>Background</h3><div>Hydroxymethylglutaryl-coenzyme A (HMGCR) inhibitors, known as statins, as first-line lipid-lowering therapies for cardiovascular diseases. Despite their widespread use, concerns persist regarding potential cognitive adverse effects, although a definitive causal relationship remains elusive.</div></div><div><h3>Methods</h3><div>To investigate the underlying mechanisms, this study integrated network toxicology, in vitro experiments, public RNA-sequencing data, computational simulations, and Mendelian randomization analysis. Rosuvastatin was chosen as a representative statin, with human as the focused species and the HMC3 human microglial cell line as the <em>in vitro</em> model.</div></div><div><h3>Results</h3><div>Network toxicology initially identified microglia as a critically involved cell type. A multi-method approach then demonstrated that rosuvastatin alters microglial functions—including cell viability, migration, phagocytosis, and inflammatory responses—potentially by the JAK-STAT signaling pathway.</div></div><div><h3>Conclusions</h3><div>These findings suggest that rosuvastatin-induced disruption of microglial function may contribute to cognitive impairment. Our study elucidates potential pathways for this adverse effect and provides novel insights for developing preventive and therapeutic strategies.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103405"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197807","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 long-acting anticoagulant rodenticide brodifacoum induces neuropathology in adult New Zealand White rabbits and is reduced by the bile sequestrant cholestyramine","authors":"Intakhar Ahmad ,&nbsp;Jacqueline Rocha ,&nbsp;Zachary McDonald ,&nbsp;Douglas L. Feinstein","doi":"10.1016/j.neuro.2026.103396","DOIUrl":"10.1016/j.neuro.2026.103396","url":null,"abstract":"<div><div>Previous studies showed that exposure to long-acting anticoagulant rodenticides (LAARs) can induce neuropathology in adult rats. In the current study we tested if the potent LAAR brodifacoum similarly promoted neuropathology in adult rabbits which provide a better model of human LAAR poisoning. Adult male New Zealand White rabbits were administered by gavage a single administration of brodifacoum at its LD₅₀ dose (200 μg/kg), followed by daily injections of vitamin K1 to prevent mortality due to anti-coagulation. After 3 weeks, examination of the cerebellum revealed an increase in glial cell activation, and a decrease in myelin content. A targeted lipidomics analysis was carried out to determine if brodifacoum altered the relative abundance of lipids enriched in myelin. We observed brodifacoum-dependent decreases in several sulfatides which were associated with an increase in expression of arylsulfatase A which degrades sulfatides. Daily treatment with the bile sequestrant cholestyramine, which accelerates LAAR clearance from the body, ameliorated brodifacoum -induced damage. These findings confirm that, despite daily vitamin K1 treatment, LAARs such as brodifacoum can induce neuropathology in adult animals and support the use of agents such as bile sequestrants to ameliorate those consequences.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103396"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106596","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":"Linking particulate matter exposure and neurological disorders: Evidence from epidemiology, biomarkers and mechanistic studies","authors":"Saiyami Bhardwaj ,&nbsp;Abhishek Bharti ,&nbsp;Radhey Shyam Sharma ,&nbsp;Santosh Kumar Mishra ,&nbsp;Pankaj Kumar ,&nbsp;Abdul S. Ethayathulla ,&nbsp;Atinderpal Singh ,&nbsp;Vandana Mishra","doi":"10.1016/j.neuro.2025.103375","DOIUrl":"10.1016/j.neuro.2025.103375","url":null,"abstract":"<div><div>Exposure to particulate matter (PM) including fine (PM₂.₅), coarse (PM₁₀), and ultrafine particles (UFPM) has emerged as a critical environmental determinant of neurological disorders, including Alzheimer’s and Parkinson’s diseases, neurodevelopmental impairments, and cognitive decline. This review integrates evidence from 129 research articles (2002–2025) to elucidate the mechanistic, biomarker-based, and public health dimensions of PM-induced neurotoxicity. Mechanistic pathways include oxidative stress, neuroinflammation, mitochondrial dysfunction, and blood–brain barrier disruption, with documented structural and functional damage in brain regions such as the hippocampus and prefrontal cortex. PM₂.₅ serves as a carrier of neurotoxic metals (e.g., lead, cadmium, vanadium) and understudied organic toxicants (e.g., PAHs, pesticides), amplifying its pathogenic potential. Exposure occurs through the olfactory route, systemic circulation, and gut–brain axis, highlighting multiple entry points into the central nervous system. Biomarkers such as Aβ₄₂, phosphorylated tau (p-tau), and α-synuclein are elevated in experimental models, but require greater validation in human PM-exposed populations. Children and older adults represent the most vulnerable groups due to developmental sensitivity and cumulative neuroinflammatory burden, yet remain underrepresented in cohort studies. Geographic disparities further limit generalizability, with low- and middle-income countries underrepresented despite experiencing the highest PM burdens. Future research must advance longitudinal, cohort and life-course studies, multi-omics biomarker discovery, and real-world mixture toxicology to identify intervention targets. These findings call for urgent integration of air pollution control into public health strategies targeting neurological diseases, emphasizing prevention through regulation, early detection, and equity-focused research frameworks.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103375"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892646","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":"Single-cell transcriptomics reveals the mechanism of long-term neurodevelopmental toxicity following sevoflurane anesthesia","authors":"Jinnan Xu ,&nbsp;Ziyu Wang ,&nbsp;Hao Wang ,&nbsp;Hongbo Wen ,&nbsp;Zhirou Wen ,&nbsp;Longying Chen ,&nbsp;Yanyong Cheng ,&nbsp;Jia Yan ,&nbsp;Hong Jiang","doi":"10.1016/j.neuro.2026.103402","DOIUrl":"10.1016/j.neuro.2026.103402","url":null,"abstract":"<div><div>Prolonged exposure to general anesthetics during early development has been associated with neurobehavioral deficits. Sevoflurane, a commonly used pediatric anesthetic, may disrupt cortical maturation, particularly in the prefrontal cortex (PFC) which plays a critical integrative and regulatory role in cognitive and motor functions. In this study, the long-term effects of neonatal sevoflurane exposure were examined using a mouse model, complemented by analysis of single-cell RNA sequencing data from human embryonic PFC (GSE196239). Behavioral assays showed that mice exposed to sevoflurane at postnatal day 7 exhibited persistent impairments in fine motor ability and spatial memory in adulthood. Transcriptomic analysis showed that sevoflurane induced widespread gene expression alterations without changing the major cell-type composition. Through enrichment analysis, dysregulation of pathways related to cell shape was identified. Consistent with these transcriptomic findings, reduced dendritic complexity was observed in sevoflurane-treated neurons by immunofluorescence. Notably, microtubule-associated protein 2 (MAP2), a key structural protein in dendrites, was significantly reduced at the protein level without a corresponding decrease in mRNA expression, suggesting the involvement of post-transcriptional regulation. Together, these findings suggest that prolonged neonatal sevoflurane exposure may impair neuronal maturation and dendritic architecture, and provide molecular insights into the long-term cognitive and motor alterations associated with neonatal sevoflurane exposure.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103402"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195386","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 aggravated neuroinflammation and oxidative stress in neonatal mice by modulating microglia phenotype via circRNA2092/miR-873a-5p/KEAP1","authors":"Yanan Li ,&nbsp;Juan Du ,&nbsp;Jiajie Zhang ,&nbsp;Zhenzhen Cai ,&nbsp;Lei Shi ,&nbsp;Jia Liang ,&nbsp;Qi Zhang","doi":"10.1016/j.neuro.2026.103410","DOIUrl":"10.1016/j.neuro.2026.103410","url":null,"abstract":"<div><div>Repeat sevoflurane exposure can cause developmental neurotoxicity while its underlying mechanism is still ambiguous. Contemporary research has increasingly highlighted the regulatory role of non-coding RNAs (ncRNAs) in the development of neurological diseases, particularly neurodegenerative conditions. However, the potential involvement of ncRNAs in sevoflurane-induced neurotoxicity remains poorly understood. In the current study, our comprehensive analysis of competing endogenous RNAs (ceRNAs) networks has identified circleRNA (circRNA) 2092 as a pivotal modulator in repetitive sevoflurane-mediated cognitive impairment, regulating microglia oxidative stress through the inhibition of microRNA miR-873a-5p and the promotion of Kelch-like ECH associating protein 1(KEAP1) expression. Notably, either knockdown of circRNA2092 and KEAP1 or administration of miR-873a-5p and Resveratrol (Oxidative stress inhibitor) could reverse the neurotoxicity of sevoflurane. Collectively, these findings demonstrate that repetitive sevoflurane exposure leads to long-term cognitive impairment in neonatal mice by aggravating microglial oxidative stress and neuroinflammatory response via the circRNA2092/miR-873a-5p/KEAP1 axis.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103410"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317868","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":"Taurine modulates gut microbiota and attenuates inflammation in a rotenone-induced mouse model of Parkinson's disease","authors":"Yunbo Zhu ,&nbsp;Shuo Wang ,&nbsp;Shuang Zhao ,&nbsp;Yujia Zeng ,&nbsp;Jing Li ,&nbsp;Pingyue Wang ,&nbsp;Zhijie Dou ,&nbsp;Tianjun Wang","doi":"10.1016/j.neuro.2026.103401","DOIUrl":"10.1016/j.neuro.2026.103401","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a prevalent neurodegenerative disorder in which gut microbiota play a critical role in pathogenesis through the gut–brain axis. Taurine has been reported to exhibit neuroprotective properties. In this study, we employed a rotenone-induced mouse model of PD to investigate the protective effects of taurine and elucidate its underlying mechanisms. PD model mice exhibited weight loss and impaired motor function, both of which were significantly ameliorated by taurine treatment. These mice also showed a marked reduction in dopaminergic neurons alongside increased microglial and astrocyte activation in the substantia nigra. Taurine preserved dopaminergic neuron numbers and suppressed glial activation. Elevated plasma levels of LPS, IL-1β, IL-6, and TNF-α were detected in the PD model group, accompanied by intestinal barrier dysfunction, blood–brain barrier disruption, and gastrointestinal impairment. Taurine administration significantly reduced pro-inflammatory cytokine levels, improved gastrointestinal motility, and preserved the integrity of both the intestinal and blood–brain barriers. Fecal microbiota analysis revealed significant compositional alterations in PD mice. Both α- and β-diversity analyses indicated profound microbial dysbiosis in the model group, which was effectively mitigated by taurine.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103401"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142992","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":"Gallic and ascorbic acids either alone or combined contribute to ameliorating lead-induced cerebral neurotoxicity in rats: A histological and immunohistochemical study","authors":"Lamiaa M. Shawky ,&nbsp;Ahmed A. Morsi ,&nbsp;Nermine Beshara ,&nbsp;Omar T. Abualnasr ,&nbsp;Ghena Hamza ,&nbsp;Lamia Asali ,&nbsp;Faten Asali ,&nbsp;Eman El Bana","doi":"10.1016/j.neuro.2026.103395","DOIUrl":"10.1016/j.neuro.2026.103395","url":null,"abstract":"<div><div>Lead (Pb) toxicity is a great community health problem. Brain is the primary target organ of Pb intoxication. Ascorbic acid (AA) and Gallic acid (GA) have proven to show potential anti‑inflammatory and antioxidant properties during heavy metal intoxication. So, the current paper aimed to explore the possible protection of AA, GA, and their combination in the current model of Pb neurotoxicity. Fifty-six Wistar male albino rats were assigned into seven groups: control, AA alone (10 mg/kg, oral), GA alone (20 mg/kg, oral), Pb alone (40 mg/kg, intraperitoneal), AA/Pb, GA/Pb, and AA/GA/Pb combination groups. After one month of oral treatment, the animals were humanely killed, and brain cortical samples were extracted for biochemical measurement of the inflammatory and oxidative markers in the brain tissue homogenates. Moreover, the samples were subjected to structural and ultrastructural examinations using light and electron microscopic (EM) studies. Pb resulted in brain injury indicated by remarkable structural and ultrastructural changes evident by neuronal degeneration and reduction of healthy nerve cells. EM showed atrophic nerve cells with irregular outlines, swollen, rarefied mitochondria, and enlarged, fused electron-dense lysosomes indicating possible autophagic vacuoles. Also, a significant increase in the pro-inflammatory markers was noticed, as evident by the raised immunohistochemical expression of glial fibrillary acidic protein (GFAP), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α). In addition, the anti-inflammatory marker decreased, as denoted by the decline in superoxide dismutase (SOD) and catalase. All these alterations were lessened by AA and GA with great restoration in the AA/GA combination group, which showed almost normal histological, ultrastructural, and biochemical parameters. AA and GA are suggested to alleviate Pb‑induced neurotoxicity owing to the modulation of oxidative stress, inflammation, and apoptosis. However, the AA/GA combination shows the greatest effect as evidenced by biochemical, structural, and ultrastructural analyses.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103395"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078703","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 miR-378a-3p/SLC7A11 axis mediates benzo[a]pyrene-induced ferroptosis in hippocampal neuronal cells","authors":"Fang Wang ,&nbsp;Xuanying Shi ,&nbsp;Xuetian Gao ,&nbsp;Dongxin Li ,&nbsp;Youquan Guo ,&nbsp;Li Chang ,&nbsp;Yu Wang","doi":"10.1016/j.neuro.2026.103406","DOIUrl":"10.1016/j.neuro.2026.103406","url":null,"abstract":"<div><div>Ferroptosis, an iron-dependent form of regulated cell death, contributes to polycyclic aromatic hydrocarbon (PAH)-induced neurodegeneration. Benzo[<em>a</em>]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, induces ferroptosis in neuronal cells, but the molecular mechanisms remain unclear. We examined the association between PAH exposure and SLC7A11 promoter methylation in human peripheral blood. Additionally, we employed molecular and genetic methods (RT-PCR, SLC7A11 knockdown/overexpression, and miR-378a-3p inhibition) to validate BaP-induced ferroptosis in HT22 neurons through the miR-378a-3p/SLC7A11 axis. The results indicated that high PAH exposure significantly reduced the average methylation level of the SLC7A11 promoter region, and BaP exposure induced ferroptosis in HT22 cells. Notably, SLC7A11 knockdown exacerbated ferroptosis, while SLC7A11 overexpression or miR-378a-3p inhibition attenuated ferroptosis. Our study therefore establishes the miR-378a-3p/SLC7A11 axis as a crucial mechanism in BaP-induced neuronal ferroptosis, providing a novel mechanistic insight into BaP-induced neurotoxicity. Targeting the miR-378a-3p/SLC7A11 pathway may mitigate environmental pollutant-induced neuronal damage in neurodegenerative diseases.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103406"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227618","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":"Longitudinal changes in pallidal index and their associations with urinary manganese and CaNa₂EDTA chelation","authors":"Tuğba Akkale ,&nbsp;Nuriye Kayalı Şendur ,&nbsp;Süleyman Filiz ,&nbsp;Nilüfer Merve Çelik","doi":"10.1016/j.neuro.2026.103397","DOIUrl":"10.1016/j.neuro.2026.103397","url":null,"abstract":"<div><h3>Objectives</h3><div>In this study, the evaluation of the change in pallidal index (PI) (ΔPI) between baseline and follow-up magnetic resonance imaging; the examination of the relationship between ΔPI and spot urine manganese (Mn) levels and baseline PI values; and the investigation of the possible effect of CaNa₂EDTA chelation therapy administered during the follow-up period on pallidal Mn accumulation were aimed.</div></div><div><h3>Methods</h3><div>In 27 participants monitored due to occupational Mn exposure, right and left PI were measured from T1-weighted images using standard protocols. ΔPI was calculated as the difference between the baseline and follow-up measurements. During CaNa₂EDTA treatment, whole blood and spot urine Mn levels were measured on the first day of each treatment course and on rest days, while 24-hour urinary Mn levels were assessed on the third day of treatment<strong>.</strong> In individuals treated with CaNa₂EDTA, the pre- and post-treatment change in PI was evaluated as a secondary analysis. Associations between ΔPI and Mn biomarkers were analyzed using the Spearman rho coefficient.</div></div><div><h3>Results</h3><div>It was determined that both right and left PI significantly decreased during the follow-up period. A negative correlation was found between spot urine Mn levels and ΔPI (right: ρ = –0.59; left: ρ = –0.45; p &lt; 0.05), indicating that the reduction in PI is more limited in individuals with higher current exposure. The positive correlation of ΔPI with the initial PI (right: ρ = 0.51; left: ρ = 0.74; p &lt; 0.05) suggests that the initial accumulation level is a determining factor in the amount of reduction. Following CaNa₂EDTA treatment, blood Mn levels significantly</div><div>Decreased in parallel with the observed reduction in PI.</div></div><div><h3>Conclusion</h3><div>PI is a dynamic imaging biomarker sensitive to changes in Mn accumulation, reflecting both the exposure level and the response to chelation therapy. The integration of MRI-based measurements with biological exposure markers can provide significant contributions to the monitoring and evaluation of treatment efficacy in populations exposed to Mn.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103397"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170366","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":"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":"2026-03-01","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}