Neurotoxicology最新文献

{"title":"Early life perfluorooctanoic acid exposure induces long-lasting effects on social behaviors in adult mice","authors":"Yue Zhang ,&nbsp;Na Qin ,&nbsp;Yutong Wang ,&nbsp;Hao Feng ,&nbsp;Zhengxin Zhang ,&nbsp;Chen Wang ,&nbsp;Zihan Qin ,&nbsp;Huiling Duo ,&nbsp;Xi Yin ,&nbsp;Yun Shi ,&nbsp;Haishui Shi","doi":"10.1016/j.neuro.2025.103323","DOIUrl":"10.1016/j.neuro.2025.103323","url":null,"abstract":"<div><div>Perfluorooctanoic acid (PFOA), a persistent organic pollutant widely used in the field of medicine, industry and agriculture, has been linked to various adverse health risks. However, the potential effects of early-life exposure to PFOA on social behaviors in adulthood remain unclear. ICR mice were exposed to different doses of PFOA (0, 1, 3 mg/kg) in drinking water for three weeks during the postweaning period. The open field test (OFT), social dominance test (SDT), novel object recognition (NOR) test, social interaction test (SIT) and social novelty preference (SNP) test were conducted to evaluate social behaviors. Behavioral results showed that postweaning PFOA exposure significantly decreased social dominance of both male and female mice during adulthood. PFOA exposure also reduced social interaction and improved social novelty in male mice, while impaired memory only in female mice. Results of 16S rRNA sequencing analysis showed the alpha-diversity, β-diversity and composition of gut microbiota altered after PFOA exposure. Following PFOA exposure, the abundance of beneficial bacteria such as Lactobacillus decreased specifically in female mice, whereas harmful bacteria such as Desulfovibrio increased in both male and female mice. Several pathways altered were predicted according to Kyoto Encyclopedia of Genes and Genomes (KEGG). The study reveals that postweaning exposure to PFOA has enduring effects on several social behaviors with variations dependent on sex, which may be linked to alterations in gut microbiota composition.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103323"},"PeriodicalIF":3.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086578","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":"EphA/EphrinA5 signaling pathway involved in the abnormal synaptic remodeling and neurotoxicity caused by benzo[a]pyrene","authors":"Xin Li ,&nbsp;Shuang Zhou ,&nbsp;Xiaoling Zhou ,&nbsp;Jinfeng Zhang ,&nbsp;Na Xia ,&nbsp;Yangyang Li ,&nbsp;Zhanfei Song ,&nbsp;Hongmei Zhang","doi":"10.1016/j.neuro.2025.103319","DOIUrl":"10.1016/j.neuro.2025.103319","url":null,"abstract":"<div><div>Benzo[<em>a</em>]pyrene (B[<em>a</em>]P) is recognized as a highly neurotoxic contaminant, however, the underlying mechanisms remain poorly understood. This study aimed to examine the alterations in erythropoietin-producing hepatocyte receptors (EphA4, EphA5) and their ligands (Ephrin A5) in the context of B[<em>a</em>]P-induced neurotoxicity, both <em>in vivo</em> and <em>in vitro</em>. A total of forty male mice were administered intraperitoneal injections of either a solvent (peanut oil) or a B[<em>a</em>]P solution (at doses of 0.5, 2, and 10 mg/kg) over a period of 60 days, once every other day. Following 30 exposures, the mice were subjected to exploratory behavioral assessments, transmission electron microscopy for hippocampal ultrastructural alterations, and western blotting to measure synapse-associated proteins (SYP, PSD95), as well as EphA4, EphA5, and Ephrin A5 proteins in the cerebral cortex. Parallel experiments were conducted using HT22 hippocampal neuronal cells. The results indicated that B[<em>a</em>]P treatment led to impairments in spatial cognitive function and spontaneous behavior, abnormal synaptic remodeling, and reduced SYP and PSD95 protein levels. Notably, compared to the control group, there was a marked increase in the protein levels of EphA4 and EphA5 in the cerebral cortex of mice following B[<em>a</em>]P treatment at mid and high doses, while Ephrin A5 protein level was significantly depressed at high dose. Additionally, in HT22 cells treated with B[<em>a</em>]P (0, 0.2, 2, and 20 μM) for 48 h, both cell viability and cell numbers exhibited a significant decline, accompanied by abnormal neuronal synaptic remodeling. In comparison to the control cells, EphA4 and EphA5 protein levels were significantly elevated in HT22 cells following B[<em>a</em>]P treatment, whereas Ephrin A5 protein levels were notably suppressed. These findings suggest that B[<em>a</em>]P may induce neurotoxicity through the disruption of synaptic remodeling via the EphA/EphrinA5 signaling pathway.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103319"},"PeriodicalIF":3.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058502","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 nasal microbiome, inhalation exposure, and brain toxicity: A commentary","authors":"Christine Frieke Kuper ,&nbsp;Eva A.J. Rennen ,&nbsp;Wolfgang Kaufmann","doi":"10.1016/j.neuro.2025.103320","DOIUrl":"10.1016/j.neuro.2025.103320","url":null,"abstract":"<div><div>The microbiome is increasingly discussed in diseases of the nervous system. The nasal microbiome is largely unexplored in neurotoxicity, while inhalation exposure to xenobiotics has been associated with neurodegenerative diseases linked to neurodegenerative diseases that are a growing health problem. The concept of a link between pathological changes of the nasal microbiome (dysbiosis) and brain neurotoxicity upon inhalation exposure is still in its early stages. In this commentary we argue that research into the nasal microbiome offers a great opportunity to obtain important information about the neurotoxicity of inhaled xenobiotics.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103320"},"PeriodicalIF":3.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065280","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":"Prenatal BPB/BPAF exposure induces depression-like behavior in male mice offspring via compound-specific transcriptional dysregulation and neurodevelopmental pathway alterations","authors":"Nannan Chen ,&nbsp;Yuetong Liu ,&nbsp;Yiran Zhouguo ,&nbsp;Xueyi Cai ,&nbsp;Xinyi Pan ,&nbsp;Rui Guo ,&nbsp;Wei Yan","doi":"10.1016/j.neuro.2025.103322","DOIUrl":"10.1016/j.neuro.2025.103322","url":null,"abstract":"<div><div>The neurodevelopmental toxicity of bisphenol A (BPA) and its substitutes has garnered significant attention. However, the association between two widely detected environmental contaminants—BPAF and BPB—and adolescent depression, along with their underlying mechanisms, remain largely unclear. Here, we established a prenatal BPB/BPAF exposure animal model and demonstrated that such exposure induces depression- and anxiety-like behaviors in weanling male offspring. Through RNA sequencing of cortical tissues, combined with screening of depression-associated transcription factors (TFs), functional enrichment analysis of target genes, and identification of hub genes, we revealed that BPB and BPAF drive disease progression via distinct transcriptional regulatory networks and biological processes. Specifically, BPB significantly downregulate the TFs Lhx8 and Foxp1, targeting hub genes (e.g., <em>Alb, Apoa1, Apoa2, Fga, Serpina1b, Fos, Rassf6, Rassf10, Rassf7, Moap1</em>) to disrupt neuropeptide-, synapse-, transcription- related biological processes. In contrast, BPAF significantly upregulate the TF Neurod1, which modulate hub genes (<em>e.g., Rpl26, Mrpl3,Rpl35, Mrpl1, Kcnd3</em>) involved in neuronal cell body and cerebral cortex development. Molecular docking further confirmed potential binding interactions between BPB and Lhx8/ Foxp1, as well as BPAF and Neurod1, mediated by hydrogen bonding or hydrophobic interactions. These findings demonstrate that BPB and BPAF induce depression-like behavior in male offspring through compound-specific disruption of transcriptional networks, which alter neurodevelopmental pathways, potentially due to their divergent binding affinities to distinct TFs. This research offers new perspectives on the neurodevelopmental toxicity associated with BPA alternatives, offering critical implications for risk assessment and therapeutic targeting of BPAF/BPB-related neuropsychiatric disorders.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103322"},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046314","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":"Ellagic acid’s dual targeting of Dmt1 uptake and Nrf2 defense counters juvenile manganese neurotoxicity","authors":"Tolulope T. Arogundade ,&nbsp;Oluwatomisin Idowu ,&nbsp;George Sanyaolu ,&nbsp;Favour E. Uware ,&nbsp;Favour O. Akinbohun ,&nbsp;Oluwatosin Popoola ,&nbsp;Olutayo Arogundade ,&nbsp;Oluwasegun D. Olatomide ,&nbsp;Emmanuel Yawson ,&nbsp;Olawande Bamisi ,&nbsp;Adedamola A. Bayo-Olugbami ,&nbsp;Habeebulahi A. Abdur-Rahman ,&nbsp;Ezra Lambe ,&nbsp;Rukayat Gbadamosi ,&nbsp;Dayo R. Omotoso ,&nbsp;Ismail Gbadamosi","doi":"10.1016/j.neuro.2025.103321","DOIUrl":"10.1016/j.neuro.2025.103321","url":null,"abstract":"<div><div>Manganese (Mn) is an environmental neurotoxicant that threatens paediatric health through contaminated water. We evaluated the potential of ellagic acid (EA), a dietary polyphenol in nuts/berries, against multi-organ Mn toxicity. Juvenile male rats (<em>n</em> = 35) were divided into: control (distilled water), Mn (100 mg/kg MnCl₂), EA (30 mg/kg), vehicle, and Mn+EA groups. After 28 days of oral treatment, behavioral tests (OFT, EPM, ART) were conducted. Tissues were analyzed for oxidative stress (SOD, CAT, MDA), neuroinflammation (TNF-α), dopamine, AChE, gene expression (DMT1, Nrf2, Sod1), and histopathology. Mn induced locomotor deficits, anxiety-like behaviour, sensorimotor hyper-reactivity, oxidative stress (↓SOD/CAT, ↑MDA), elevated TNF-α, and reduced dopamine. EA co-treatment reversed behavioural impairments, restored antioxidant activity, normalized TNF-α/dopamine, EA suppressed Mn-induced Dmt1 upregulation, a key compensatory Mn uptake pathway in juveniles, while activating Nrf2, representing a novel dual protective mechanism. Histology confirmed EA preserved neuronal integrity and reduced hepatorenal damage. In conclusion, EA-associated downregulation of Dmt1 and downstream biochemical/histological improvements provide indirect evidence consistent with reduced Mn influx, but requires confirmation by direct brain Mn quantification.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103321"},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic cisplatin treatment in young mice induces long-term complications in the peripheral nervous system in a sex-dependent manner","authors":"Laura Yanneth Ramírez-Quintanilla,&nbsp;Santos Adrián Pérez-Reyes,&nbsp;Martin de Jesus Salazar-Hernández,&nbsp;Héctor Fabián Torres-Rodríguez,&nbsp;Virginia Margarita Vargas-Muñoz,&nbsp;Ana Rebeca García-Araujo,&nbsp;Rosa Issel Acosta-González,&nbsp;Enriqueta Muñoz-Islas,&nbsp;Juan Miguel Jiménez-Andrade","doi":"10.1016/j.neuro.2025.103318","DOIUrl":"10.1016/j.neuro.2025.103318","url":null,"abstract":"<div><div>Cisplatin-induced peripheral neuropathy (CIPN) is one of the most prevalent long-term complications in pediatric cancer survivors reaching adulthood. However, very few studies have evaluated the long-term effects of cisplatin administered to the young population on the peripheral nervous system and assessed whether these effects are sex-dependent. Thus, we aimed to assess baseline mechanical withdrawal thresholds (a CIPN measurement), the density of CGRP⁺ and PGP9.5⁺ axons in the glabrous skin, changes in different markers in DRG, and determine pain-like responses after intra-plantar capsaicin in female and male mice at 4 weeks after cessation of cisplatin. Four-week-old BALB/c mice were treated with cisplatin (4 mg/kg, intraperitoneally, twice weekly for 4 weeks). Four weeks after cessation of cisplatin, these mice, at 12 weeks of age, exhibited significant hindpaw mechanical hypersensitivity, which was greater in magnitude in female mice compared to male mice. At 13 weeks old, cisplatin-treated mice also had a greater density of CGRP⁺ and PGP9.5⁺ intraepidermal nerve fibers compared to saline-treated groups in female and male mice, independent of sex. The number of CGRP⁺ and ATF3⁺ neuronal profiles and CD68⁺ monocyte/macrophage in L4 DRG was higher in cisplatin-treated mice than in saline-treated mice, independent of sex. Intra-plantar capsaicin injection in adult mice resulted in greater and longer flinching and guarding behaviors in cisplatin-pretreated mice compared to saline-pretreated mice. The enhanced capsaicin-induced pain behaviors were significantly greater in female compared to male mice. These findings demonstrate long-term, partially sex-related complications in the peripheral nervous system following cisplatin treatment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103318"},"PeriodicalIF":3.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical doses of gadodiamide have no damaging effects on cochlear tissue in vitro and in vivo","authors":"Xiong Zhang ,&nbsp;Jingwen Zhang ,&nbsp;Yang Tian ,&nbsp;Yixi Xiao ,&nbsp;Hengkang He ,&nbsp;Jing Luo ,&nbsp;Dalian Ding ,&nbsp;Hai Liu ,&nbsp;Jianhui Zhang","doi":"10.1016/j.neuro.2025.103317","DOIUrl":"10.1016/j.neuro.2025.103317","url":null,"abstract":"<div><div>Gadolinium-based contrast agents (GBCAs) are widely used in systemic magnetic resonance imaging (MRI) and can be employed in otology to evaluate endolymphatic hydrops in patients with Ménière’s disease. Given the heavy metal properties of gadolinium and its tendency to deposit in tissues, it is essential to assess its ototoxic risk. We evaluated the ototoxicity of gadodiamide using <em>in vitro</em> and <em>in vivo</em> models. <em>In vitro</em>, cochlear explants from postnatal day 3 rats were cultured for 24 h in medium containing 0, 100 (equivalent to the concentration in perilymph after intratympanic injection), 500, or 2500 μM gadodiamide. Immunofluorescence results revealed that no significant structural damage occurred to hair cells (HCs) or spiral ganglion neuron (SGN) somata at any concentration, and that only the 2500 μM group exhibited slight thinning or disintegration of auditory nerve fibers (ANFs). <em>In vivo</em>, 50 μL of normal saline, 8-fold diluted, or undiluted gadodiamide was applied to the round window membrane (RWM) of adult rats via a postauricular approach. Evaluation 5 days later showed that, compared with the saline group, there were no significant changes in the compound action potential (CAP) thresholds or cochlear structures in rats treated with either 8-fold diluted or undiluted gadodiamide. The results confirmed that clinical doses of gadodiamide do not cause damage to cochlear structures; however, the neurotoxicity observed at excessively high concentrations highlights the necessity of strict adherence to dosing protocols.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103317"},"PeriodicalIF":3.9,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030174","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":"Monoamine depletion and oxidative imbalance underlie ketamine-induced motor deficits in adolescent rats","authors":"Natália Harumi Corrêa Kobayashi ,&nbsp;Lucas Villar Pedrosa da Silva Pantoja ,&nbsp;Brenda Costa da Conceição ,&nbsp;Marta Eduarda Oliveira Barbosa ,&nbsp;Sabrina de Carvalho Cartágenes ,&nbsp;Pedro Iuri Castro da Silva ,&nbsp;Jofre Jacob da Silva Freitas ,&nbsp;Geanne Matos de Andrade ,&nbsp;Enéas Andrade Fontes-Junior ,&nbsp;Bruno Gonçalves Pinheiro ,&nbsp;Cristiane do Socorro Ferraz Maia","doi":"10.1016/j.neuro.2025.103316","DOIUrl":"10.1016/j.neuro.2025.103316","url":null,"abstract":"<div><div>Ketamine has been widely used as a recreational substance by adolescents and young adults in nightclubs and raves in an acute manner, especially during the weekend. Considering the scarcity of evidence on the harmful consequences of adolescent ketamine recreational use on the central nervous system, primarily related to motor function, this study aimed to investigate the behavioral, biochemical, and neurochemical consequences on motor function induced by ketamine use, evaluating the motor cortex, cerebellum, and striatum in early abstinence. Adolescent female Wistar rats (28 days old) received ketamine by intranasal route (10 mg/kg/day) for 3 consecutive days. Twenty-four hours following the ketamine protocol, the animals were subjected to behavioral tests in the open field, inclined plane, pole, and rotarod tests. After behavioral assays, the animals were anesthetized and euthanized for the collection of the motor cortex, cerebellum, and striatum for biochemical and monoamine evaluations. We found that ketamine exposure in early adolescence induced a reduction in spontaneous locomotion, motor imbalance, and bradykinesia associated with oxidative stress and a decrease in neurotransmitter levels, particularly dopamine, norepinephrine, and serotonin in the striatal region. These results demonstrate that ketamine recreational use in a binge pattern in the early adolescence period displays a widespread motor function impairment during the first periods of withdrawal, which oxidative damage in motor areas and neurotransmitter reduction in the striatum may contribute to the behavioral alteration observed.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103316"},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015827","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":"Cholinergic dysfunction in occupational manganese exposure","authors":"T. Noah Hutson ,&nbsp;Susan Searles Nielsen ,&nbsp;Natalie Senini ,&nbsp;John O’Donnell ,&nbsp;Hubert P. Flores ,&nbsp;Tamara Hershey ,&nbsp;Joel S. Perlmutter ,&nbsp;Anil Kumar Soda ,&nbsp;Stephen M. Moerlein ,&nbsp;Zhude Tu ,&nbsp;Michael Kasper ,&nbsp;Lianne Sheppard ,&nbsp;Brad A. Racette ,&nbsp;Susan R. Criswell","doi":"10.1016/j.neuro.2025.103313","DOIUrl":"10.1016/j.neuro.2025.103313","url":null,"abstract":"<div><h3>Background and objective</h3><div>Excessive exposure to manganese (Mn) produces a clinical syndrome of parkinsonism and cognitive impairment. However, our understanding of the mechanisms of Mn neurotoxicity remains limited. This study aimed to evaluate the relationships between Mn exposure, cholinergic function, and cognitive impairment in exposed workers.</div></div><div><h3>Methods</h3><div>We assessed brain cholinergic function using vesicular acetylcholine transporter (VAChT) radiotracer (-)-(1-(8-(2-[(18)F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone (VAT) with positron emission tomography (PET) in 21 Mn-exposed workers. We estimated occupational Mn exposure from work histories and the MRI pallidal index. A cognitive control battery consisting of the Verbal Fluency (VF), Letter Number Sequencing (LNS), Two-Back Letter Task (2B), Go-No-Go (GnG), and Simon Task assessed cognitive function. We applied generalized linear models to Mn exposure, voxel-based cholinergic PET, and cognitive control measures, estimating coefficients for cholinergic-mediated associations between Mn and cognitive function. We utilized bootstrapping techniques to validate the mediation coefficients.</div></div><div><h3>Results</h3><div>Both Mn exposure metrics were associated with low cholinergic VAT binding in the caudate and cortical regions including the precuneus, pars triangularis, pars opercularis, middle temporal lobe, and entorhinal cortex. Regional cholinergic function mediated the relationship between Mn exposure and both the composite cognitive control score (mean of the 5 cognitive tests) [β = -0.661, 90 % confidence interval (CI) −2.130, −0.032] and the individual VF assessment (β = −0.944, 90 % CI −2.157, −0.065).</div></div><div><h3>Discussion</h3><div>Higher Mn exposure is associated with lower cholinergic activity in multiple brain regions. Cholinergic function also mediates a portion of the relationship between Mn exposure and cognitive control performance. Caudate and cortical cholinergic activity may be a biomarker of early Mn neurotoxicity and represent an important mechanism of cognitive dysfunction in parkinsonian syndromes.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103313"},"PeriodicalIF":3.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006383","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":"Altered development in rodent brain cells after 900 MHz radiofrequency exposure","authors":"Raphaël Bodin ,&nbsp;Lucas Godin ,&nbsp;Camille Mougin ,&nbsp;Anthony Lecomte ,&nbsp;Vanessa Larrigaldie ,&nbsp;Justyne Feat-Vetel ,&nbsp;Sarah Méresse ,&nbsp;Céline Montécot-Dubourg ,&nbsp;Paulo Marcelo ,&nbsp;Stéphane Mortaud ,&nbsp;Anne-Sophie Villegier","doi":"10.1016/j.neuro.2025.103312","DOIUrl":"10.1016/j.neuro.2025.103312","url":null,"abstract":"<div><div>Health risks related to 900 MHz 2 G frequency exposure remain inconclusive under current regulatory standards. Research into potential long-term effects is ongoing, particularly as the use of mobile networks and wireless devices increases. This study investigates the effects of non-thermal exposure levels of mobile phone 900 MHz radiofrequency electromagnetic field (RF-EMF) on rodent neurodevelopment. <em>In vivo</em>, the effects of pre- and post-natal 0.08 and 0.4 W/kg specific absorption rate (SAR) exposure were assessed for their impact on the proteomic profile at postnatal day 0 (PND 0). Brain-derived neurotrophic factor (BDNF), BrdU+ proliferative cells, synaptogenesis, and oxidative stress in the hippocampus and cortex of rat pups were studied at PND 8 and PND 17. Effects of the lowest SAR (0.08 W/kg) were assessed <em>in vitro</em> to afford mechanistic data regarding neural stem cells (NSCs) differentiation. <em>In vivo</em> results showed a decrease in BDNF level and BrdU+ proliferative cells with a decrease in synapse balance (excitatory synapses/inhibitory synapses). <em>In vitro</em>, at 0.08 W/kg there was an increase in Ki-67 + proliferative cells, apoptosis, and double-strand DNA breaks in NSCs. A lower ratio of B1 cells (primary progenitors of NSCs) among total cerebral cells and a higher ratio of oligodendrocyte progenitor cells and astrocytes were observed in the exposed NSCs. Our findings suggest that key cellular events for brain ontogenesis are likely to undergo changes with RF-EMF 900 MHz exposure during early development. These support the hypothesis that the developing central nervous system is vulnerable to RF-EMF exposures in rodents at regulatory thresholds.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"111 ","pages":"Article 103312"},"PeriodicalIF":3.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989013","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}