Neurotoxicology最新文献

{"title":"Postnatal particulate matter exposure alters developmental milestones and brain gene expression in apoE transgenic mice in a sex- and genotype-dependent manner","authors":"Rocío Rodulfo-Cárdenas ,&nbsp;Judit Biosca-Brull ,&nbsp;Séfora Barberà-Parada ,&nbsp;Raquel Gabaldón-Díaz ,&nbsp;Diego Ruiz-Sobremazas ,&nbsp;Jordi Blanco ,&nbsp;Maria Cabré ,&nbsp;José L. Domingo ,&nbsp;Caridad López-Granero ,&nbsp;Fernando Sanchez-Santed ,&nbsp;Maria Teresa Colomina","doi":"10.1016/j.neuro.2026.103466","DOIUrl":"10.1016/j.neuro.2026.103466","url":null,"abstract":"<div><div>Air pollution, with particulate matter (PM) as one of its most critical environmental contaminants, represents a major global health threat and a leading cause of premature mortality. PM can reach the central nervous system (CNS) and has been implicated in both neurodevelopmental and neurodegenerative disorders. Individual susceptibility to PM-induced neurotoxicity is shaped by genetic background. Apolipoprotein E (APOE), the major CNS apolipoprotein, plays a key role in brain homeostasis and neurodevelopment, and its isoforms may differentially modulate vulnerability to environmental insults. However, the interaction between <em>APOE</em> genotype and PM exposure during early development remains poorly understood. We aimed to investigate the developmental effects of early postnatal PM exposure in humanized apoE3 and apoE4 transgenic mice. From postnatal day (PND) 4–14, pups underwent daily whole-body inhalation exposure to Fine Atmospheric PM (SRM 2787, NIST), with a nominal theoretical chamber concentration of 3789 µg/m³. Physical milestones, neuromotor performance, and sexual maturation were monitored until PND42. Forebrain and cerebellum samples were analyzed for genes involved in neurotransmission, neurotrophic signaling, and neuroinflammation. Postnatal PM exposure reduced weight gain in females and impaired neuromotor performance. Furthermore, it accelerated eye and vaginal opening in apoE3 mice. The effects of PM exposure on gene expression were more pronounced in apoE4 mice, including alterations in GABAergic (<em>Nkcc1</em>), glutamatergic (<em>Grin2b</em>), serotonergic (<em>5ht2c</em>), and neurodevelopmental (<em>Reln</em>) markers. These findings indicate that early postnatal PM exposure disrupts neurodevelopment through sex- and genotype-specific mechanisms and support APOE genotype as a modifier of vulnerability to PM-induced developmental neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103466"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931319","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":"Preliminary evidence of polyvinyl chloride microplastics inducing ferroptosis in the cerebral cortex of ducks","authors":"Li Wang ,&nbsp;Hongsheng Song ,&nbsp;Tao Wang ,&nbsp;Yan Chen ,&nbsp;Yonggang Ma ,&nbsp;Xishuai Tong ,&nbsp;Hui Zou ,&nbsp;Jianhong Gu ,&nbsp;Xuezhong Liu ,&nbsp;Jianchun Bian ,&nbsp;Zongping Liu ,&nbsp;Yan Yuan","doi":"10.1016/j.neuro.2026.103467","DOIUrl":"10.1016/j.neuro.2026.103467","url":null,"abstract":"<div><div>Ferroptosis, a type of regulated cell death, is frequently observed in mammalian brain cortical injuries and diseases linked to iron metabolism disorders. Recent evidence suggests that microplastic exposure may trigger such ferroptosis-related pathologies. However, the mechanism and impact of ferroptosis-induced cerebral cortex damage in waterfowl due to microplastic exposure remain unclear. In this study, Muscovy ducks were divided into three groups receiving: pure water, 1 mg·L⁻¹ polyvinyl chloride microplastics (PVC-MPs), or 10 mg·L⁻¹ PVC-MPs for two months. This study suggests that PVC-MPs may accumulate in the duck cerebral cortical tissue, where they disrupt blood-brain barrier (BBB) integrity as manifested by ultrastructural damage and significant downregulation of tight junction protein levels (ZO-1, Occludin, and Claudin-5). Moreover, PVC-MPs exposure induced histopathological and nuclear ultrastructural damage, along with oxidative stress and excessive iron accumulation, both hallmarks of ferroptosis. Specifically, PVC-MPs triggered mitochondrial cristae fragmentation and shrinkage, as well as lipid peroxidation accumulation, evidenced by elevated MDA levels. Western blot analysis confirmed ferroptosis through significant downregulation of SLC7A11, GPX4, and FTH1, and upregulation of COX2. In conclusion, this study suggests that PVC-MPs may accumulate in the duck cerebral cortex, where they disrupt BBB integrity and induce histopathological damage, as well as disturb redox homeostasis and trigger ferroptosis, ultimately leading to neuronal injury.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103467"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931558","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":"Disruption of hippocampal synaptic plasticity by chronic ethanol exposure: A narrative review of neurotoxic adverse outcome pathways","authors":"Fatemeh Seyedi ,&nbsp;Mahdiyeh Hedayati-Moghadam ,&nbsp;Mojgan Heidari ,&nbsp;Ahmad Golkar ,&nbsp;Yousef Baghcheghi","doi":"10.1016/j.neuro.2026.103465","DOIUrl":"10.1016/j.neuro.2026.103465","url":null,"abstract":"<div><div>Chronic is a major neurotoxicant that disrupts hippocampal synaptic plasticity, leading to persistent cognitive deficits. This narrative review maps the adverse outcome pathways (AOPs) through which ethanol impairs synaptic function, primarily via interconnected cascades: TLR4/NF-κB-mediated neuroinflammation (triggering microglial activation and pro-inflammatory cytokines TNF-α, IL-1β), CYP2E1-driven oxidative stress (generating ROS/RNS, 4-HNE, causing protein carbonylation and mitochondrial dysfunction), and glutamate excitotoxicity (mediated by GluN2B-NMDAR subunit shifts, Ca²⁺ overload, and astrocytic EAAT2/GLT-1 downregulation). These pathways converge to suppress BDNF/TrkB signaling (via miR-206 and impaired proBDNF cleavage), leading to deficits in synaptic protein synthesis (e.g., Arc) and trafficking (e.g., GluA1 endocytosis via STEP, impaired forward trafficking). Critically, these insults potentiate neuronal apoptosis through intrinsic (ROS/mitochondrial permeabilization, caspase-9/-3) and extrinsic (TNF-α/TNF-R1, caspase-8) pathways, executing irreversible synaptic loss via caspase-3 cleavage of PSD-95, spectrin, and cytoskeletal collapse. The structural consequences—dendritic simplification, reduced mature spine density, and PSD-95 nano-domain disorganization—manifest functionally as attenuated LTP, potentiated mGluR-LTD, and impaired STDP. This synaptic decay directly underpins cognitive impairments in pattern separation, contextual memory, and cognitive flexibility. Neuroinflammation (TLR4/NF-κB) acts as a central amplifier, linking oxidative damage, excitotoxicity, and BDNF collapse to apoptotic synaptic deletion. Future research must address dose-dependency, subfield vulnerability, epigenetic regulation, and therapeutic strategies targeting TLR4, TrkB, mitochondrial antioxidants, and anti-apoptotic pathways.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103465"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931251","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":"Gut microbiota: A critical regulator of oxaliplatin-induced peripheral neurotoxicity development","authors":"Zhen Liu ,&nbsp;TingRong Zhang ,&nbsp;SiMin Wang ,&nbsp;HuaFang Yin ,&nbsp;XiaXia Shao ,&nbsp;LingJuan Gao ,&nbsp;XiangDong Lu","doi":"10.1016/j.neuro.2026.103460","DOIUrl":"10.1016/j.neuro.2026.103460","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Oxaliplatin-induced peripheral neuropathy (OIPN) is a common dose-limiting toxicity that significantly affects patients’ quality of life. Although neuroinflammation has been implicated, the precise contribution of the gut–nerve axis remains incompletely understood. This study aimed to investigate the role of gut microbiota and associated inflammatory signaling in OIPN.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An OIPN model was established in Sprague Dawley rats. Gut microbiota depletion was achieved via antibiotic (ABX) treatment, and fecal microbiota transplantation (FMT) from healthy donors was performed to restore microbial communities. Mechanical allodynia and cold hypersensitivity were assessed using the von Frey filament test and the acetone test, respectively. Systemic inflammation was evaluated by measuring serum cytokine levels via enzyme-linked immunosorbent assay (ELISA). The composition of the gut microbiota was analyzed by 16S rRNA gene sequencing. Intestinal barrier integrity and local inflammation were assessed through histopathology, immunofluorescence, and quantification of tight junction proteins (ZO-1, occludin) and inflammatory markers (NF-κB, TNF-α) via quantitative polymerase chain reaction (qPCR) and Western blotting. Network pharmacology was employed to screen for potential common targets of oxaliplatin and neurotoxicity. Molecular alterations in the dorsal root ganglia (DRG) were examined using histology, qPCR, Western blotting, and immunofluorescence, with a focus on the TLR4/MyD88/NF-κB signaling pathway and pro-inflammatory cytokines.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Antibiotic-mediated depletion of gut microbiota significantly attenuated OXA-induced neuropathic pain and systemic inflammation, as evidenced by reduced levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β), whereas FMT reversed these protective effects. Analysis of 16S rRNA gene sequencing revealed that OXA altered gut microbiota composition, including reduced alpha diversity, altered beta diversity, a decreased Firmicutes/Bacteroidetes ratio, and taxonomic changes. These alterations were partially restored following FMT under the present experimental conditions. Functional prediction analysis indicated enrichment of the lipopolysaccharide (LPS) biosynthesis pathway. Consistently, OXA treatment was associated with elevated LPS levels in plasma and feces, which were reduced by ABX treatment and increased following FMT. OXA was also associated with impaired intestinal barrier integrity, as evidenced by decreased expression of ZO-1 and Occludin and increased inflammatory markers (NF-κB, TNF-α) in the colon, changes that were modulated by microbiota status. Network pharmacology analysis identified inflammation-related pathways and potential targets. In the DRG, OXA treatment was associated with neuronal injury, increased expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and ","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103460"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777286","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":"Best practices in neurotoxicology research must account for spontaneous brain malformations in rodent models","authors":"Justin T. Popp,&nbsp;Raddy L. Ramos","doi":"10.1016/j.neuro.2026.103474","DOIUrl":"10.1016/j.neuro.2026.103474","url":null,"abstract":"<div><div>Spontaneous neocortical and cerebellar heterotopia are present in rat and mouse strains commonly used in neurotoxicology research. These malformations reflect neuronal migration defects during neocortical and cerebellar development that are inherent in these strains, yet the influence of these heterotopia are not considered in the design and interpretation of neurotoxicology research. In this review, we describe anatomical, behavioral, and physiological studies relevant to spontaneous neocortical and cerebellar heterotopia in rats and mice. This work will inform researchers in possible design and assessment approaches to account for these malformations which will likely be present in both control and exposure-treated groups.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103474"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043186","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":"Adverse effects and mechanisms induced by legacy, emerging per- and polyfluoroalkyl substances on neuron: Human exposure, adverse outcomes","authors":"Rencan Zeng ,&nbsp;Guanghua Mao ,&nbsp;Yao Chen ,&nbsp;Hai Xu ,&nbsp;Yangyang Ding ,&nbsp;Ting Zhao ,&nbsp;Liuqing Yang ,&nbsp;Xiangyang Wu ,&nbsp;Dan Wang ,&nbsp;Weiwei Feng","doi":"10.1016/j.neuro.2026.103459","DOIUrl":"10.1016/j.neuro.2026.103459","url":null,"abstract":"<div><div>Per- and polyfluoroalkyl substances (PFASs), due to their distinctive physicochemical characteristics, are emerging pollutants that are widely used as raw materials in industrial production, leading to their ubiquitous presence in the environment, plants and animals. Humans may also face health risks from exposure to PFASs. This paper reviews that the different populations are exposed to PFASs in their daily lives through diet, drinking water, indoor air, and assess the health risks to susceptible populations from various exposure pathways. Research has shown that PFASs can persist in organisms for a long time and can cross the blood-brain barrier, accumulating in the brain. Additionally, experimental studies on animals have demonstrated the occurrence of neurodevelopmental toxicity induced by PFASs, including behavioral problems, alterations to neurotransmitters, and brain tissue lesions. Epidemiological studies have demonstrated that PFASs are associated with adverse outcomes in susceptible populations, including cognitive function, learning, memory, and motor function. Finally, this paper elucidates the potential mechanisms from the perspectives of disrupted signaling pathways, synaptic plasticity, and endocrine disruption. It demonstrates that PFASs may alter neuronal synaptic structures, leading to abnormal neurotransmitter secretion and affecting intracellular calcium homeostasis and calcium signaling. It is hoped that this review will provide a reference for further research on the neurodevelopmental toxicity and health risks of PFASs.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103459"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777312","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":"Simulated wildfire smoke particulate matter elicits STING-dependent astrocyte-mediated inflammatory signaling and neurotoxicity","authors":"Adam J. Schuller ,&nbsp;Abigail M. Bibb ,&nbsp;Megan R. Hager ,&nbsp;Omar A. Yanouri ,&nbsp;Emma J. Smith ,&nbsp;Aidan M. Briggs ,&nbsp;Luke B. Montrose ,&nbsp;Ronald B. Tjalkens","doi":"10.1016/j.neuro.2026.103473","DOIUrl":"10.1016/j.neuro.2026.103473","url":null,"abstract":"<div><div>Changing global wildfire landscapes necessitate exploration of the effects of exposure to wildfire smoke on health and disease. Exposure to this toxicant is not only associated with acute cardiopulmonary dysfunction, but is increasingly recognized as a serious risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the cellular and molecular mechanisms which underlie this association are not well understood. One potential mechanism linking neurotoxic environmental exposures with neurodegeneration is glial-mediated neuroinflammation, which may be influenced by innate immune signaling through the cGAS-STING pathway in response to damaged or mislocalized DNA. To address this hypothesis, we here exposed primary astrocyte-enriched mixed glial cultures to laboratory generated wildfire smoke particulate matter extract and subsequently examined their reactivity and inflammatory signaling by applying cutting-edge techniques in high content microscopy, deep learning-based image analysis, and transcriptomics. We found that wildfire smoke exposure elicits DNA damage and results in STING signal transduction in astrocytes, including the production and release of inflammatory cytokines, as well as STING-dependent neurotoxicity. To better understand the mechanisms underlying this phenomenon, we integrated transcriptomic data from <em>in vitro</em> and <em>in vivo</em> wildfire smoke exposures studies, which revealed central hubs for functional enrichment surrounding interferon signaling. Together, these data strongly identify STING signaling as a central modulator of astrocyte-mediated inflammation resulting from wildfire smoke exposure.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103473"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033452","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":"Comparing effects of gaseous vs. particulate components of traffic-related air pollution on Alzheimer’s disease biomarkers in a genetically susceptible rat model","authors":"Nathifa Nasim ,&nbsp;Mei-Yun Cheng ,&nbsp;Heui Hye Park ,&nbsp;Anthony Valenzuela ,&nbsp;Peter Andrew ,&nbsp;Anthony S. Wexler ,&nbsp;Vidya Chandrasekaran ,&nbsp;Laura S. Van Winkle ,&nbsp;Keith Bein ,&nbsp;Pamela J. Lein","doi":"10.1016/j.neuro.2026.103472","DOIUrl":"10.1016/j.neuro.2026.103472","url":null,"abstract":"<div><div>Epidemiological data link traffic-related air pollution (TRAP) to increased risk of Alzheimer’s disease (AD) and AD-related dementia (ADRD), and while experimental animal studies corroborate this association, most utilized exposure paradigms that failed to recapitulate the complexity of current, real-world TRAP exposure. Furthermore, the specific components of TRAP that promote AD pathogenesis remain unknown. This study assesses AD-relevant pathology in a transgenic rat model of AD (TgF344-AD) following chronic exposure to the gas phase vs. particulate matter (PM) components of TRAP in emissions from light-duty only (LDV) vs. combined light- and heavy-duty (LDV+HDV) vehicles. Male and female TgF344-AD rats were transported to the Caldecott Tunnel Exposure Facility (CTEF) at 1 month of age after being randomly assigned to one of six exposure groups: (1) filtered air (FA), (2) LDV+HDV gases only; (3) LDV PM only; (4) LDV+HDV PM only; (5) LDV PM and gases; and (6) LDV+HDV PM and gases. AD-relevant endpoints were quantified in 4-, 9-, 12-, and 15- month-old animals. Cortical Aβ levels at the 4, 9, and 15-month timepoints were significantly influenced by sex-by-exposure interactions. Amyloid plaque accumulation in the entorhinal cortex and hippocampus exhibited significant sex-dependent effects at 9 and 12 months so males and females were analyzed separately across all timepoints. At 9 months, females exposed to LDV+HDV PM had increased amyloid plaques in the hippocampus, and at 15 months, both females and males exposed to LDV PM and females exposed to LDV PM and gases exhibited significantly increased plaque levels in the entorhinal cortex. The rate of plaque accumulation over all four time points was accelerated in the entorhinal cortices of both sexes exposed to LDV and LDV+HDV PM alone or in combination with gases. There were no exposure effects on phosphorylated tau or Thioflavin S staining; however, the rate of neuronal cell loss with increasing age was significantly increased by exposure to LDV emissions in both females and males. Collectively, these findings demonstrate that chronic exposure to ambient TRAP in real-time promoted AD-relevant outcomes in the TgF344-AD rat with effects that varied according to age, sex, and brain region. TRAP effects occurred more prominently in groups exposed to LDV PM. Further research is needed to determine the mechanism(s) by which sex-dependent TRAP effects exacerbate AD pathogenesis so that effective interventions can be developed to improve the health of the aging brain.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103472"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043137","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":"Ozone in neurodegeneration: An environmental toxicant or a therapeutic hormetin?","authors":"Caterina Vinciguerra ,&nbsp;Mariangela Cernera ,&nbsp;Marika Comegna ,&nbsp;Maria Rosaria Amoroso ,&nbsp;Giulia Renata Franco ,&nbsp;Loredana Bellia ,&nbsp;Francesca De Stefano ,&nbsp;Antimina Castaldo ,&nbsp;Graziamaria Corbi ,&nbsp;Giuseppe Rengo ,&nbsp;Alessandro Cannavo","doi":"10.1016/j.neuro.2026.103471","DOIUrl":"10.1016/j.neuro.2026.103471","url":null,"abstract":"<div><div>Ozone (also known as triatomic oxygen [O₃]) is an allotropic form of oxygen commonly found in the atmosphere. Growing epidemiological and experimental evidence indicates that chronic exposure to environmental ozone (as a pollutant) may worsen systemic disorders, including neurodegenerative processes. Prolonged exposure to atmospheric uncontrolled ozone increases pulmonary production of reactive oxygen and nitrogen species, triggering oxidative damage and a sustained inflammatory state locally and systemically, and leading to multiple alterations, including blood–brain barrier breakdown and microglial dysfunction, mechanisms strongly implicated in neurodegenerative processes. Interestingly, ozone therapy (controlled and non-inhaled) has been used in medicine for its multiple health benefits, including antimicrobial, anti-inflammatory, and antioxidant effects. Thus, it is plausible to consider ozone as a hormetin with potential neuroprotective effects. Additionally, experimental evidence showing its effects in nerve regeneration, including improved structural and functional recovery following facial or sciatic nerve injury, further strengthens the potential of ozone therapy. However, further studies are required to define optimal dosing strategies and administration protocols. Given these findings, the scope of this review is to critically examine and integrate all available evidence on ozone’s dual role in neurological and neurodegenerative conditions. By combining mechanistic insights, preclinical and clinical data, this review aims to clarify the complex, bidirectional relationship among ozone exposure, redox biology, neuroinflammation, and neurodegeneration.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103471"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987812","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":"Early postnatal exposure to permethrin and deltamethrin mixtures induces sex-specific hippocampal neurobehavioral and neurochemical alterations in adulthood","authors":"Sabrine Ben Slimene ,&nbsp;Khadija Boukholda ,&nbsp;Rahma Ammar ,&nbsp;Chloé Aman ,&nbsp;Anne-Emilie Allain ,&nbsp;Philippe De Deurwaerdère ,&nbsp;Ons Boudawara ,&nbsp;Abdeslam Chagraoui ,&nbsp;Michèle Bouchard ,&nbsp;Hamadi Fetoui","doi":"10.1016/j.neuro.2026.103468","DOIUrl":"10.1016/j.neuro.2026.103468","url":null,"abstract":"<div><div>Pyrethroid insecticides, including deltamethrin and permethrin, are known for their individual toxic effects; however, evidence regarding their combined toxicity during early developmental stages remains limited. The present study aimed to investigate the neurotoxic effects of co-exposure to deltamethrin and permethrin in lactating rats, focusing on emotional and cognitive behaviors, as well as cholinergic and monoaminergic neurotransmission in their progeny at adulthood (5 months of age). Dams were orally administered deltamethrin (1.35 mg/kg/day) and permethrin (34 mg/kg/day), either individually or in combination, from postnatal day (PND) 7 to PND 21. Our results demonstrated that co-exposure of lactating females to deltamethrin and permethrin induced behavioral alterations in their offspring, including impaired locomotor activity, anxiety-like behavior, and learning and memory deficits, with sex-specific effects. Furthermore, these toxicants triggered oxidative stress in the hippocampus, as indicated by elevated levels of malondialdehyde, nitric oxide, and advanced oxidation protein products, along with impaired enzymatic and non-enzymatic antioxidant defenses. Early postnatal exposure also caused sex-dependent modifications in monoamine concentrations across multiple brain regions. Mechanistically, molecular alterations of the cholinergic system were observed in the hippocampus of both male and female rats, as evidenced by downregulation of AChE, mAChR, and nAChR gene expression. These molecular changes were further confirmed by histological analyses. In conclusion, our findings demonstrate that exposure of lactating females to deltamethrin and permethrin, individually or in combination, induces sex-dependent, deleterious, and sometimes distinct neurodevelopmental effects in their offspring at PND 150.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103468"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006220","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}