Neurotoxicology最新文献

{"title":"CD4 + T cell activation and peripheral immune cell influx into the brain following wildfire smoke exposure is modulated by a saturated fat diet.","authors":"Brenna Baird, Justin R Carter, Ember Suh, Russell Hunter, Jorge L Moreno, Milad MazloumiBakhshayesh, Alicia M Bolt, Marian Olewine, Ed Barr, Jessica Begay, Selita Lucas, Yan Jin, Ximeng Liu, Lingjun Li, Shiquan Cui, Haiwei Gu, Matthew J Campen, Shahani Noor","doi":"10.1016/j.neuro.2026.103589","DOIUrl":"10.1016/j.neuro.2026.103589","url":null,"abstract":"<p><p>Over the past 40 years, wildfires across the United States have steadily increased, in terms of acreage burned. Smoke from wildfires can exacerbate several cardiovascular and respiratory diseases, with new studies highlighting potential sustained neurological outcomes. The purpose of this study was to delineate the role of peripheral immune populations in woodsmoke-induced neuroinflammation, the timeline of this response, and the impact of diet on each of these factors. Based on previous research on other pollutants and diet introduction, we included a highly saturated fatty acid (coconut oil) to represent the effects of a diet intervention that may modulate the severity and time course of peripheral immune infiltration. 8-week-old female C57BL/6 mice were exposed to either a sham filtered air or a woodsmoke exposure of a 0.5 mg/m³ concentration every other day for 14 days, 4 hr/day. Three time points were analyzed: 1-, 14-, and 28-days post exposure to woodsmoke to determine neuroinflammation at its peak and when it begins to resolve. At each time point, brains were queried by high dimensional flow cytometry analysis. Markers for peripheral immune infiltration included T cells (CD3, CD4), lymphocyte trafficking (LFA-1), resident immune cells (CD11b, ACSA-2) and other inflammation-dependent markers. Endothelial cell populations (CD31) and relevant adhesion molecules (VCAM-1, ICAM-1) were also analyzed. Results demonstrate a time and diet-dependent influx of CD4 T cells (Cd11b^-, CD3⁺, CD4⁺, RORγ^-, FOXP3^-, CD44⁺), potentially to resolve neuroinflammation from woodsmoke inhalation. We also see a pattern of inflammation across several trafficking and adhesion markers, including LFA-1, VCAM-1 and ICAM-1, that peaks at 1 day after the last exposure (14 days after the initial insult). Conferred with these results are metabolomic changes in the brain including upregulated taurine and glycerolipid metabolism that is mainly tied to increased susceptibility to inflammatory phenotypes in the brain. Here, we demonstrate that woodsmoke inhalation can initiate the recruitment of peripheral immune populations and activation of endothelial cell markers within the brain. The presence of these cells implicates a larger, more persistent impact on the central nervous system following woodsmoke exposure.</p>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":" ","pages":"103589"},"PeriodicalIF":3.8,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216440","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":"Keap1/Nrf2 mediated ferroptosis in early-life lead exposure-induced cognitive dysfunction in mice","authors":"Feiyu Zhao,&nbsp;Liming Huang,&nbsp;Binbin Yang,&nbsp;Ruokun Wei,&nbsp;Fan Qiao,&nbsp;Zihao Qi,&nbsp;Huishuai Li,&nbsp;Zhenning Li,&nbsp;Yuanyuan Fang,&nbsp;Dongjie Peng,&nbsp;Shaojun Li","doi":"10.1016/j.neuro.2026.103554","DOIUrl":"10.1016/j.neuro.2026.103554","url":null,"abstract":"<div><h3>Background</h3><div>Early-life lead (Pb) exposure has been confirmed to cause long-term cognitive impairment, but the mechanisms of its programmed cell death remain incompletely elucidated. This study aims to investigate the key role of Nrf2-mediated ferroptosis in early-life Pb exposure-induced cognitive impairment in mice.</div></div><div><h3>Methods</h3><div>By employing both in vivo and in vitro approaches, we explored the involvement of Keap1/Nrf2-mediated ferroptosis in early-life Pb exposure-induced cognitive impairment.</div></div><div><h3>Results</h3><div>Our findings showed that early-life Pb exposure induced ferroptosis by upregulating hippocampal Keap1 expression and inhibiting the Nrf2 pathway and its downstream antioxidant proteins (GPX4, SLC7A11, and SLC3A2), and altering the expression of iron metabolism-related proteins (downregulating FTH1/FTL and upregulating DMT1). This process led to ferroptosis, as evidenced by elevated levels of the lipid peroxidation product MDA and reduced glutathione peroxidase activity. Furthermore, this process was accompanied by upregulation of the neurodegeneration-related protein APP in hippocampal tissues, which ultimately resulted in neurodegenerative lesions.</div></div><div><h3>Conclusion</h3><div>This study reveals the mechanism of Keap1/Nrf2-mediated ferroptosis in cognitive dysfunction induced by early-life Pb exposure, providing a potential therapeutic strategy targeting this pathway to alleviate Pb exposure-associated neurodegenerative lesions.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"116 ","pages":"Article 103554"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813526","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":"An integrative model of ketamine-induced memory dysfunction: From synapse to circuit in clinical context","authors":"Mola Mohammadi,&nbsp;Amin Saeedi,&nbsp;Ali Asghar Kheirkhah Vakilabad,&nbsp;Fatemeh Seyedi,&nbsp;Ahmad Golkar,&nbsp;Yousef Baghcheghi","doi":"10.1016/j.neuro.2026.103558","DOIUrl":"10.1016/j.neuro.2026.103558","url":null,"abstract":"<div><div>Ketamine presents a modern pharmacological paradox, acting as both a rapid-acting antidepressant and a drug of abuse with significant cognitive consequences. While its therapeutic potential is revolutionary, chronic exposure is increasingly associated with persistent and specific deficits in episodic and working memory. This narrative review moves beyond descriptive lists of ketamine's effects to propose a novel integrative model that delineates the coherent pathophysiological cascade through which chronic ketamine exposure induces memory dysfunction. We synthesize evidence that the initiating event—NMDA receptor antagonism, particularly on GABAergic interneurons—triggers a glutamate surge and glutamatergic dysregulation. This initial insult activates a self-reinforcing and pathological amplifying loop of neuroinflammation (e.g., microglial activation, cytokine release) and oxidative stress (e.g., mitochondrial dysfunction, ROS/RNS generation). These converging insults subsequently suppress BDNF/TrkB neurotrophic signaling and cause synaptic disintegration, impairing the plasticity mechanisms that underlie learning and memory. The cascade structurally culminates in apoptotic neuronal deletion, which permanently degrades the cellular substrate within critical memory circuits. This molecular and cellular pathology ultimately manifests as systems-level dysfunction, specifically the functional disconnection of the hippocampus-prefrontal cortex axis, explaining the core clinical memory deficits. By bridging evidence from synapse to circuit, this integrative model provides a unified framework for understanding individual vulnerability, proposes biomarkers for personalized risk assessment, and identifies targeted neuroprotective strategies to mitigate cognitive harm while preserving ketamine's therapeutic benefits.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"116 ","pages":"Article 103558"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860578","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":"Erratum to “Air pollution is linked to divergent cortical thickness patterns in brain regions vulnerable to Alzheimer’s disease” [Neurotoxicology 115 (2026) 103495]","authors":"Lauren E. Salminen,&nbsp;Xinhui Wang,&nbsp;Andrew J. Petkus,&nbsp;Christine Fennema-Notestine,&nbsp;Jeremy A. Elman,&nbsp;Donald J. Hagler Jr,&nbsp;Joel D. Kaufman,&nbsp;Joshua Millstein,&nbsp;Meredith N. Braskie,&nbsp;Joshua Liu,&nbsp;Hyung Jin Cho,&nbsp;Deydeep Kothapalli,&nbsp;Paul M. Thompson,&nbsp;Daniel P. Beavers,&nbsp;Mark A. Espeland,&nbsp;Margaret Gatz,&nbsp;Susan M. Resnick,&nbsp;Ira Frahmand,&nbsp;Stephen R. Rapp,&nbsp;Caleb E. Finch,&nbsp;Carol E. Franz","doi":"10.1016/j.neuro.2026.103551","DOIUrl":"10.1016/j.neuro.2026.103551","url":null,"abstract":"","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"116 ","pages":"Article 103551"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Long-term effects of polychlorinated biphenyls: Neuropsychological outcomes of a longitudinal cohort study” [Neurotoxicology 116 (2026) 103507]","authors":"Julia Luka Cromberg,&nbsp;Thomas Schettgen,&nbsp;Klaus Willmes,&nbsp;Jessica Lang,&nbsp;Thomas Kraus,&nbsp;Bruno Fimm","doi":"10.1016/j.neuro.2026.103534","DOIUrl":"10.1016/j.neuro.2026.103534","url":null,"abstract":"","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"116 ","pages":"Article 103534"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory transcriptomic and network-based analysis of methylmercury exposure in human neuronal developmental models using GEO datasets and toxicogenomic resources","authors":"Danna Gomez-Caballero,&nbsp;Jesus Olivero-Verbel","doi":"10.1016/j.neuro.2026.103488","DOIUrl":"10.1016/j.neuro.2026.103488","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Methylmercury (MeHg) is a well-recognized environmental neurotoxicant with a marked impact on neurodevelopment. However, studies integrating stage-specific transcriptomic responses in human neuronal development remain limited.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study aimed, in an exploratory manner, to integrate and compare transcriptomic profiles induced by MeHg across distinct stages of human neuronal development, in order to evaluate shared and differential transcriptional responses among models representing early neuroepithelial differentiation, neural progenitor expansion, and mature neuronal function.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;MeHg-associated genes were retrieved from the Comparative Toxicogenomics Database (CTD), GeneCards, and PubChem. Three human transcriptomic datasets from GEO were analyzed, corresponding to early neuroepithelial differentiation (UKN1), neural progenitor expansion (hNPT), and mature dopaminergic neurons (LUHMES). Differentially expressed genes were identified using GEO2R. Integrated analyses included protein–protein interaction network construction, hub gene identification using centrality algorithms in Cytoscape, and functional enrichment, transcription factor, and disease ontology analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Integration of databases identified a set of four genes (CASP3, GPX1, MT2A, and SOD2) consistently present across all resources. Differential expression analysis across the three neuronal models revealed both shared and model-specific transcriptional responses to MeHg exposure. A conserved set of three overexpressed genes (BRD7, HSPH1, and MCM5) was identified across all models, whereas no common repressed gene signature was observed across the three systems, although partial overlaps were detected between pairs of models. Network analysis highlighted central genes associated with general stress-related processes, including apoptosis, oxidative stress, and inflammatory signaling. Functional enrichment analyses indicated activation of broad cellular stress response pathways, with additional enrichment in processes related to cell cycle regulation and genome maintenance. Disease ontology analysis showed enrichment in broad disease categories, without evidence supporting disease-specific mechanistic interpretation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This integrative transcriptomic and network-based analysis provides an exploratory framework to prioritize candidate genes and biological processes associated with methylmercury exposure across human neuronal developmental models. The results indicate consistent involvement of general stress-related processes but do not support the identification of specific mechanisms or universal regulatory patterns across models. The absence of a conserved repression signature further highlights transcriptional heterogeneity among developmental stages. Overall, these findings should be interpreted as hypothesis-g","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"115 ","pages":"Article 103488"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212032","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":"Bioinformatics and experimental insights into the relationship between ferroptosis and fluoride-induced neurotoxicity","authors":"Qinyang Qin,&nbsp;Yuhui Du,&nbsp;Xinying Wang,&nbsp;Leizhen Duan,&nbsp;Yi Cheng,&nbsp;Weihua Jia,&nbsp;Wenyi Liu,&nbsp;Xi Yan,&nbsp;Fangfang Yu,&nbsp;Yue Ba,&nbsp;Guoyu Zhou","doi":"10.1016/j.neuro.2026.103496","DOIUrl":"10.1016/j.neuro.2026.103496","url":null,"abstract":"<div><div>Although fluoride is known to cause neurological impairment, the underlying molecular mechanisms remain unclear. Given that ferroptosis may contribute to neurotoxicity, we explored whether fluoride induces neuronal ferroptosis and sought to identify the signaling pathways involved by integrating bioinformatics analysis with experimental validation. Bioinformatics screening of 23 intersecting differentially expressed genes (DEGs) revealed significant enrichment of ferroptosis-related signaling pathways, with <em>TP53</em> as the top-ranked gene. In silico analysis further predicted three potential p53 binding sites in the <em>SLC7A11</em> promoter region. Experimentally, rats received 10, 50 and 100 mg/L NaF, and SH-SY5Y cells were treated with 20, 40 and 60 mg/L NaF. NaF-treated rats exhibited impaired performance in Morris water maze tests. Concurrently, elevated Fe^2 + and total iron were detected in NaF-treated rat brains and SH-SY5Y cells. NaF treatment also impaired antioxidant capacity and induced lipid peroxidation, increasing ROS and MDA levels while decreasing GSH levels and the GSH/GSSG ratio, confirmed by immunofluorescence and biochemical analyses <em>in vivo</em> and <em>in vitro</em>. Transmission electron microscopy revealed that NaF induced mitochondrial alterations in vitro, including a loss of cristae. At the molecular level, NaF upregulated p53 (confirmed by immunofluorescence) and ACSL4 while downregulating SLC7A11 (xCT) and GPX4 expression in rat hippocampi and cells. Notably, these pathological alterations were attenuated by the ferroptosis inhibitor Ferrostatin-1 and p53 siRNA, validating the involvement of ferroptosis and the p53/xCT/GPX4 signaling pathway. In conclusion, our findings uncover that fluoride may activate the p53/xCT/GPX4 signaling pathway, inducing neuronal ferroptosis and subsequent neurological impairment, and suggest <em>TP53</em> as a potential target gene for the control of fluoride neurotoxic effects.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"115 ","pages":"Article 103496"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278214","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 bisphenol A exposure impairs cognitive function in male mice associated with NLRP3 inflammasome-driven pyroptosis and gut microbiota dysbiosis along the microbiota-gut-brain axis","authors":"Zhongwei Tang,&nbsp;Junjie Yang,&nbsp;Xin Guo,&nbsp;Zhoujie Hao,&nbsp;Huimin Wang,&nbsp;Mohammad Mehdi Ommati,&nbsp;Jianqin Yuan","doi":"10.1016/j.neuro.2026.103498","DOIUrl":"10.1016/j.neuro.2026.103498","url":null,"abstract":"<div><div>The microbiota-gut-brain axis (MGBA) is a critical bidirectional communication system governing cognitive function and intestinal homeostasis. Despite growing evidence linking environmental chemicals to neurological disorders, the mechanisms underlying bisphenol A (BPA)-induced cognitive deficits remain poorly understood. Here, we demonstrate that chronic BPA exposure may induce cognitive impairment in male offspring through disruption of the MGBA, specifically via upregulation of the NLRP3 inflammasome/pyroptosis-related markers. Gravid Kunming mice received BPA (0, 2, 20, or 200 µg/kg body weight/day) in drinking water until weaning; their male offspring were then orally administered identical doses for nine weeks. Behavioral tests revealed significant deficits in short- and long-term memory following high-dose (200 µg/kg) BPA exposure. Mechanistically, high-dose BPA reduced hippocampal neuron density, compromised ileal barrier integrity, and induced dysbiosis characterized by decreased α-diversity (Chao1, ACE, Shannon; <em>P</em> &lt; 0.05) and an elevated <em>Firmicutes</em>/<em>Bacteroidota</em> ratio. LEfSe analysis identified increased abundance of potentially pro-inflammatory genera at 200 µg/kg. Crucially, high-dose BPA upregulated the expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-18 in both the hippocampus and ileum, alongside elevated serum TNF-α and IL-18, indicating systemic inflammation. Correlation analyses further linked specific microbial shifts to pyroptosis markers and cognitive decline. Collectively, our findings establish that chronic BPA exposure may triffer gut dysbiosis and barrier dysfunction, leading to NLRP3 inflammasome activation and pyroptotic cell death in both the gut and brain, ultimately impairing cognition. These results underscore the neurotoxic risk posed by BPA and provide a mechanistic rationale for stricter regulatory controls on its use in food-contact materials.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"115 ","pages":"Article 103498"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295645","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":"Adolescent prefrontal and amygdala molecular signatures of perinatal morphine versus buprenorphine exposure in mice","authors":"Brittany L. Smith,&nbsp;Grace Winstel,&nbsp;Brandon Brooks-Patton,&nbsp;Anna G. Makela,&nbsp;Boluwatife Osifalujo,&nbsp;Noah Raleigh,&nbsp;Bolaji Akindiose,&nbsp;Claire Mitchell,&nbsp;Maria E. Taylor,&nbsp;Kyle L. Cosby","doi":"10.1016/j.neuro.2026.103505","DOIUrl":"10.1016/j.neuro.2026.103505","url":null,"abstract":"<div><div>Buprenorphine (BUP) treatment during pregnancy reduces overdose risk and attenuates adverse neonatal outcomes compared to full μ-opioid receptor agonists. Yet, prenatal exposure to BUP and other opioids is associated with long-term executive function deficits in children. Prenatal BUP exposure also relates to reductions in neonatal amygdala volume. To assess the impact in offspring brain regions relevant to these clinical findings and in the absence of clinical confounds, we examined the effects of perinatal BUP versus morphine (MO) on the offspring prefrontal cortex (PFC) and basolateral amygdala (BLA) in adolescent mice. Female mice were given once daily s.c. injections of low dose BUP (0.1 mg/kg, n = 8), MO (10 mg/kg, n = 12), or saline (SAL, n = 10) during pre-gestation, gestation, and lactation until offspring were weaned. We conducted RNA sequencing and immunohistochemistry in the PFC and BLA at postnatal day (P)39. Offspring exploratory and social behavior were assessed, as well as puzzle box performance in early adulthood. MO increased expression of microglia markers in male offspring at the transcriptional (<em>Csf1r</em>, <em>Cx3cr1</em>, <em>P2ry12)</em> and protein (CD68, IBA1) level that was prominent in the PFC, while CD68 increases were also evident in the BLA with BUP. Female BUP offspring had the greatest numbers of differentially expressed genes, especially in the BLA. Expression patterns related to downregulation of genes involved in neuron growth and upregulation of immediate early genes. MO subtly impaired puzzle box performance in females, while MO and BUP decreased thigmotaxis behavior in the open field in males. Overall, perinatal MO exposure affects microglia markers, particularly in adolescent male offspring. The BLA may be particularly sensitive to the effects of perinatal BUP exposure despite subtle behavioral changes.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"115 ","pages":"Article 103505"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361561","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":"Gestational and lactational exposure to glyphosate and a glyphosate-based herbicide causes sex-dependent effects on neurodevelopment and monoaminergic markers in rats","authors":"Isela Hernández-Plata,&nbsp;Jair Santiago-Salazar,&nbsp;María Soledad Mendoza-Trejo,&nbsp;Jonathan Sánchez-Yépez,&nbsp;Eduardo A. Garza-Villarreal,&nbsp;Verónica M. Rodríguez","doi":"10.1016/j.neuro.2026.103500","DOIUrl":"10.1016/j.neuro.2026.103500","url":null,"abstract":"<div><div>Glyphosate (Glyph) exposure during the gestational and lactational periods have been linked to neurodevelopmental alterations in humans and animal models, and it has been proposed to induce autistic-like traits in rodents. This study evaluated the effects of gestational and lactational exposure to Glyph and a glyphosate-based herbicide (GBH) on neurodevelopmental and monoaminergic outcomes in male and female rat offspring, using valproic acid (VPA) as a pharmacological model of autism. Pregnant dams were orally treated with 50 mg Glyph/L in distilled water or with GBH throughout gestation and lactation. The VPA group received a single intraperitoneal injection of 500 mg/kg on gestational day 12.5, while controls received only distilled water. Male and female pups underwent a battery of neurodevelopmental tests from postnatal day (PND) 3–21, and brains were collected at PND 21 to assess monoaminergic markers. Offspring exposed to VPA showed alterations in early social interactions. Female pups treated with Glyph or VPA mainly exhibited reduced body weight during lactation. Delayed performance in the negative geotaxis test was observed in female pups exposed to Glyph 9, and in VPA pups at PND 5 and 9. Only male GBH-exposed pups exhibited impairments in righting reflexes on PND 7. Neurochemical analyses revealed sex-dependent alterations in dopamine, serotonin, and their metabolites in the prefrontal cortex, striatum, nucleus accumbens, ventral midbrain, hippocampus, and amygdala. These findings show that gestational and lactational exposure to low levels of Glyph or GBH induces some sexually dimorphic effects on behavior and neurochemistry, resembling those seen in ASD-like models.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"115 ","pages":"Article 103500"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148331554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}