Neurotoxicology and teratology最新文献

{"title":"Hydrogen activated the Nrf2/HO pathway to alleviate the cognitive decline in PD Drosophila after long-term sevoflurane exposure","authors":"Ming Li ,&nbsp;Bo Ma ,&nbsp;Si Liang ,&nbsp;Xuanyi Pan ,&nbsp;Jingyi Xie ,&nbsp;Hongjie Wang ,&nbsp;Jiguang Guo","doi":"10.1016/j.ntt.2025.107560","DOIUrl":"10.1016/j.ntt.2025.107560","url":null,"abstract":"<div><div>The demand for surgical and anesthetic care in patients with Parkinson's disease (PD) is projected to increase, because PD is the fastest-growing neurological disorder. Sevoflurane, the most commonly used volatile anesthetic, is neurotoxic to human and animal neonatal brains. Moreover, sevoflurane-based anesthesia can induce postoperative delirium (POD) in patients with PD. Therefore, our study was aimed at finding an effective treatment for sevoflurane-induced neurotoxicity in patients with PD by using a PD-POD <em>Drosophila</em> model. The small gas, hydrogen (H₂), was found to ameliorate learning and memory impairment, and increase the lifespan of PD flies, after long-term sevoflurane exposure. The performance index of the PD-POD flies increased by 30 % after H₂ inhalation. Moreover, H₂ inhalation decreased oxidative stress levels in PD fly brains, and increased electron transport chain and OXPHOS efficiency, as well as ATP synthesis, thus indicating enhanced mitochondrial function. In addition, PD flies with H₂ inhalation after sevoflurane exposure showed increased nuclear levels of Nrf2 and expression of its downstream target HO. Therefore, H₂ might exert antioxidant effects by activating the Nrf2/HO pathway, thereby decreasing oxidative stress levels and apoptosis in PD fly brains after long-term sevoflurane treatment. Inhalation of H₂ is likely to be an effective and convenient method to alleviate the neurotoxicity effects or POD caused by long-term sevoflurane exposure.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"112 ","pages":"Article 107560"},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252292","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":"Organophosphorus compounds and neurological conditions: Dr. Jekyll and Mr. Hyde","authors":"Eugenio Aztiria ,&nbsp;Carlos Javier Baier","doi":"10.1016/j.ntt.2025.107563","DOIUrl":"10.1016/j.ntt.2025.107563","url":null,"abstract":"<div><div>This article reviews the use, toxicology, and neurological effects of organophosphates (OPs) used as pharmacological agents. OPs, a versatile chemical family, have been applied in many sectors but pose significant risks, particularly to the nervous system. In the first part of this review, we discuss the toxicological effects of OPs, particularly their inhibition of the acetylcholinesterase (AChE) enzyme, leading to severe neurological impairments. Indeed, prolonged exposure to these chemicals can trigger neuroinflammation, oxidative stress, and changes in neurotransmitter systems, resulting in cognitive deficits, neuropsychiatric disorders, and, potentially, neurodegeneration. In the second part, we address the therapeutic potential of these chemicals, focusing mainly on their effects on the central nervous system (CNS). Some naturally occurring compounds, like citicoline, have shown neuroprotective properties, while synthetic OPs such as bisphosphonates and their derivatives are being explored to treat some mental conditions. However, the high toxicity and side effects of some of them, whether in the short or long term, may limit their use in clinical settings. Overall, there is a call for better animal models and continued research to develop safer therapeutic options.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"112 ","pages":"Article 107563"},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213141","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 association of preconception and prenatal cannabis and tobacco exposure with autism symptoms in offspring: A population-based longitudinal study","authors":"Kim N. Cajachagua-Torres ,&nbsp;Olga D. Boer ,&nbsp;Anneke Louwerse ,&nbsp;Akhgar Ghassabian ,&nbsp;Irwin K.M. Reiss ,&nbsp;Vincent W.V. Jaddoe ,&nbsp;Hanan El Marroun","doi":"10.1016/j.ntt.2025.107561","DOIUrl":"10.1016/j.ntt.2025.107561","url":null,"abstract":"<div><div>Prenatal cannabis and tobacco exposure is associated with attention and behavior problems in children, while associations with autism symptoms remain unclear. We prospectively examined whether parental cannabis and tobacco use during pregnancy were associated with childhood autism symptoms. Information on parental cannabis and tobacco use was assessed using questionnaires, and maternal cannabis metabolites were detected via urinalysis. We measured autistic symptoms using two mother-reported instruments: Child Behavior Checklist (CBCL) at ages 1.5, 3, and 6; and Social Responsiveness Scale (SRS) at 6 years (<em>n</em> = 4380). Linear mixed models were used to examine the association between parental cannabis and tobacco use and CBCL autism symptoms across childhood. Linear regression was used for SRS autism symptoms. Maternal cannabis use before, but not during, pregnancy was associated with higher CBCL autism symptoms across childhood (β: 0.33, 95 % CI: 0.02, 0.63). Paternal cannabis use was linked to higher CBCL autism symptoms across childhood (β: 0.27, 95 % CI: 0.05, 0.50), explained by maternal psychopathology; no association was found with SRS autism symptoms. Excluding cannabis users, children whose mothers used tobacco throughout pregnancy had more SRS autism symptoms (β: 0.03, 95 % CI: 0.003, 0.05), not CBCL; no association was found with paternal tobacco use.</div><div>Our results suggest that maternal and paternal cannabis use is not associated with offspring autism symptoms, although preconception use is associated with autism symptoms across childhood. In contrast, maternal continued tobacco use during pregnancy was associated with autism symptoms, but not paternal use, suggesting possible intrauterine programming rather than family-based factors.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"112 ","pages":"Article 107561"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183780","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":"Assessing replicability and power estimates of behavioral performance of control rats across standardized pre-clinical and toxicology studies","authors":"Kathryn S. Konrad ,&nbsp;Laura Betz ,&nbsp;Sandra McBride ,&nbsp;Keith R. Shockley ,&nbsp;Georgia Roberts ,&nbsp;Helen Cunny ,&nbsp;G. Jean Harry","doi":"10.1016/j.ntt.2025.107562","DOIUrl":"10.1016/j.ntt.2025.107562","url":null,"abstract":"<div><div>Behavioral assays are critical in evaluating impacts on nervous system function in rodents due to genetic or environmental factors and are frequently incorporated into regulatory decision-making studies. Despite numerous sources of guidance for such studies, results across behavioral assays are reputed to be highly variable with questionable replicability. Behavioral data obtained from control rats within four contract laboratory studies were used to evaluate replicability across studies, calculate the level of statistical power, and estimate the number of animals required for a specific effect size. For the three behaviors evaluated here (motor activity, acoustic startle response, and learning and memory), control rats from all studies showed the expected pattern of behavior, e.g., open field acclimation, startle habituation, % prepulse inhibition (PPI) over pre-pulse intensities, and acquisition and goal quadrant preference in the Morris Water Maze (MWM). For selected representative individual endpoints, power analyses were conducted to evaluate sample size requirements. Across all endpoints, a drop in power occurred as differences between two groups became smaller. Power analysis of multiple representative endpoints suggested that a sample size of 20 may detect a 30 % effect with 80 % power. Sample size requirements changed with the effect size, and achieving 80 % power with a 20 % effect size generally required a sample size of 30 rats. While the behavioral performance was replicated over the Study Cohorts, power analyses suggested a need for moderation of expectations regarding detectable differences if decisions relied on single endpoints or small effect sizes. Reporting results from a low powered study can have significant and wide-ranging impacts, including undermining confidence in data interpretation, misleading future research, and failing to adhere to the ethical framework of the 3 R's.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"112 ","pages":"Article 107562"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186615","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":"Maternal and early postnatal antibiotic exposure may increase the risk of autism spectrum disorder with regression","authors":"Boli Cheng ,&nbsp;Xi Lai ,&nbsp;Huan Liu ,&nbsp;Si Wang ,&nbsp;Xinghui Li ,&nbsp;Mei Tan ,&nbsp;Juan Liu ,&nbsp;Yun He","doi":"10.1016/j.ntt.2025.107550","DOIUrl":"10.1016/j.ntt.2025.107550","url":null,"abstract":"<div><h3>Purpose</h3><div>To analyze if exposure to antibiotics during maternal pregnancy and early postnatal period increases the risk of autism spectrum disorder with regression (ASD-R).</div></div><div><h3>Methods</h3><div>A total of 483 children with ASD were categorized into ASD-R and ASD without regression (ASD-NR) groups. The caregivers of children completed questionnaires regarding use of antibiotics during maternal pregnancy and early postnatal period.</div></div><div><h3>Results</h3><div>There were significantly higher proportions of antibiotic exposure during maternal pregnancy and before age of 2 in the ASD-R group (10.3 % and 44.0 %) compared to the ASD-NR group (2.9 % and 33.1 %). Children with ASD and maternal antibiotic exposure had a higher likelihood of experiencing regression compared to those without exposure (unadjusted OR = 3.81, 95 %CI: 1.67–8.68; adjusted OR = 3.36, 95 %CI: 1.44–7.8). Also, children with ASD who were exposed to antibiotics during early postnatal period had a higher risk of regression, as opposed to those who were not exposed (unadjusted OR = 1.59, 95 % CI 1.08–2.32; adjusted OR = 1.50, 95 % CI 1.01–2.21). Both maternal and early postnatal antibiotic exposure were associated with certain dimensions and total scores of the ABC.</div></div><div><h3>Conclusions</h3><div>The ASD-R group had higher rates of antibiotic exposure during both maternal pregnancy and the early postnatal period compared to the ASD-NR group. Maternal and early postnatal antibiotic exposure may be risk factors for regression in children with ASD. Children with ASD who were exposed to antibiotics during maternal pregnancy or the early postnatal period may have more severe core symptoms than those without such history of exposure.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"111 ","pages":"Article 107550"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932620","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":"Associations of prenatal tobacco and insecticide co-exposures with neurobehavioral responses among children born to pregnant women exposed to cannabis.","authors":"Neha Sehgal, Patricia A Brennan, Anne L Dunlop, Donghai Liang, Elizabeth J Corwin, Youran Tan, Todd M Everson, W Michael Caudle, Parinya Panuwet, Priya E D'Souza, Volha Yakimavets, Grace E Lee, Dana Boyd Barr, Stephanie M Eick","doi":"10.1016/j.ntt.2025.107536","DOIUrl":"10.1016/j.ntt.2025.107536","url":null,"abstract":"<p><strong>Background: </strong>Cannabis and tobacco are contaminated with insecticides and used during pregnancy in the U.S., raising concerns for co-exposures and compounded neurodevelopmental effects. However, these cumulative effects remain unexplored. We examine the associations of prenatal cannabis, tobacco, pyrethroid, and organophosphate insecticides co-exposures with early childhood neurobehaviors.</p><p><strong>Methods: </strong>Among 197 mother-child pairs from a birth cohort in Atlanta, Georgia, cannabis (THCCOOH), tobacco (COT and 3OH-COT), pyrethroids (3PBA), and organophosphates (TCPY) metabolite levels were quantified in maternal urine sampled at 8-14 and 24-30 weeks' gestation. Infant arousal and attention were evaluated 2 weeks postnatally using the NICU Network Neurobehavioral Assessment Scale. Externalizing and internalizing behaviors were assessed annually using the Child Behavior Checklist and averaged across ages 2-5 years. We examined individual associations using linear regression; cumulative associations using quantile g-computation and Bayesian kernel machine regression (BKMR); and whether THCCOOH modified the cumulative effect of tobacco and insecticides.</p><p><strong>Results: </strong>Of the prenatal exposures, only insecticides were associated with child neurobehavior. For example, a doubling in 3PBA was positively related to internalizing behaviors (β = 18.1 %; 95 % confidence interval [CI] = 0.0 %, 39.5 %), and TCPY was negatively associated with externalizing behaviors (β = -12.9 %; 95 % CI = -27.8 %, 5.0 %). These were modified by THCCOOH and sex. The prenatal 3PBA, TCPY, COT, and 3OH-COT mixture was associated with lower externalizing behaviors among females with detectable THCCOOH (quantile g-computation β = -46.8 %; 95 % CI = -70.4 %, -4.1 %). BKMR showed no interactions and dose-responses.</p><p><strong>Discussion: </strong>Prenatally, 3PBA and TCPY were associated with child neurobehaviors, and effects differed by THCCOOH and sex. Further studies on the neurodevelopmental burden of cannabis, tobacco, and insecticide co-exposures are needed.</p>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":" ","pages":"107536"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775880","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":"Neuroprotective and cognitive-enhancing potentials of herbal remedies: Focus on St. John's wort, green tea, and Ashwagandha","authors":"Mohamed Ahmed","doi":"10.1016/j.ntt.2025.107549","DOIUrl":"10.1016/j.ntt.2025.107549","url":null,"abstract":"<div><div>Neurodegenerative diseases and cognitive impairments represent significant global health challenges, necessitating the exploration of alternative and complementary therapeutic options. Herbal remedies, known for their bioactive compounds, have garnered attention for their potential neuroprotective and cognitive-enhancing effects. This review focuses on three widely studied herbal agents, including St. John's Wort (<em>Hypericum perforatum</em>), Green Tea (<em>Camellia sinensis</em>), and Ashwagandha (<em>Withania somnifera</em>) and evaluates their mechanisms in promoting brain health. St. John's Wort has demonstrated potential in alleviating symptoms of depression and anxiety, which are often linked to cognitive decline. Green Tea, rich in polyphenols such as epigallocatechin gallate (EGCG), has shown promise in improving memory function and providing antioxidant protection against neurotoxicity. Ashwagandha, an adaptogenic herb, is recognized for its neuroprotective properties, including reducing stress-induced cognitive deficits and promoting neuronal regeneration. The neuroprotective and cognitive-enhancing effects of these herbs are attributed to their antioxidative, anti-inflammatory, and neurotrophic properties, which collectively may support brain function and mitigate age-related cognitive decline.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"111 ","pages":"Article 107549"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932619","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":"Autism spectrum disorder-like behaviors in developing zebrafish exposed to particulate matter","authors":"Shayla Victoria,&nbsp;Courtney Roper","doi":"10.1016/j.ntt.2025.107548","DOIUrl":"10.1016/j.ntt.2025.107548","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that can impact communication and social behaviors. Evidence suggests that the causes of ASD are likely a combination of genetic and environmental factors, such as air pollution. Particulate matter (PM) is the solid and liquid portion of air pollution that can vary in size and has been associated with many health impacts, including cardiorespiratory impacts, and has more recently been found to be associated with the prevalence of ASD. However, little is known about the phenotypic presentations of this association between PM and ASD, therefore, the zebrafish (<em>Danio rerio</em>) model was employed to study behaviors often associated with ASD as a result of PM exposure. Zebrafish larvae were exposed for a total of 5 days to PM standard reference material (SRM1649b) and a commonly used home remedy, melatonin, beginning at 6 h post-fertilization and various behavioral assays were performed on subsequent days for a total of 13 days. Observed and quantified behaviors were compared to a positive control, valproic acid (VPA). Generally, PM exposure did not elicit behavior resembling that of VPA exposure and the interactions between PM and VPA did not induce additive or synergistic behavioral patterns, as expected. Melatonin supplementation did not ameliorate most of the observed behavioral impacts of PM or VPA exposure. These results have prompted additional questions about the phenotypic presentations of ASD as a result of PM exposure and contribute to growing knowledge about disease-environment interactions.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"111 ","pages":"Article 107548"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908918","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":"Extreme low-temperature exacerbates polystyrene microplastic-induced neuroendocrine and behavioral dysfunctions in female mice","authors":"Liliana Ataides Silva Barichello ,&nbsp;Rafaela Ribeiro de Brito ,&nbsp;Wesley Rodrigues Soares ,&nbsp;Aline Sueli de Lima Rodrigues ,&nbsp;Alex Rodrigues Gomes ,&nbsp;Bruno da Cruz Pádua ,&nbsp;Bruna de Oliveira Mendes ,&nbsp;Ariane Guimarães ,&nbsp;Raíssa de Oliveira Ferreira ,&nbsp;Thiarlen Marinho da Luz ,&nbsp;Guilherme Malafaia","doi":"10.1016/j.ntt.2025.107547","DOIUrl":"10.1016/j.ntt.2025.107547","url":null,"abstract":"<div><div>Despite the growing recognition of the impacts of microplastics (MPs) and the intensification of extreme weather events, recent investigations have focused mainly on the consequences of global warming, while overlooking the potential impacts of extreme low-temperature (ELT) events and their interaction with these pollutants. Accordingly, the aim of this study was to assess the integrated effects of <em>co</em>-exposure to environmentally aged polystyrene microplastics (PS-MPs) and ELTs on behavioral, neuroendocrine, metabolic, and histomorphometric biomarkers in female Swiss mice. To this end, animals were orally exposed to environmentally aged PS-MPs (10 mg/kg/day) and maintained in a climate-controlled chamber at 4 °C for 21 days, whereas control groups were kept at 25 °C. In the behavioral domain, co-exposed animals exhibited increased locomotor disorganization, anxiety-like behavior, reduced exploratory efficiency, and impairments in memory and social discrimination, associated with neuroendocrine alterations involving dopamine, serotonin, epinephrine, and corticosterone, depending on the response evaluated. The retention of PS-MPs in the interscapular brown adipose tissue (iBAT) was confirmed by epifluorescence microscopy. It was associated with oxidative stress, decreased antioxidant defenses, and metabolic dysfunction in iBAT, effects exacerbated by ELT exposure. Multivariate analyses, including principal component analysis (PCA), Random Forest, and structural equation modeling (PLS-PM), revealed distinct phenotypic patterns among groups, as well as integrated causal trajectories linking neuroendocrine dysfunction to systemic phenotypic alterations. In conclusion, our study confirms the initial hypothesis by demonstrating that the combination of ELT and PS-MP ingestion amplifies systemic physiological dysfunctions beyond the effects of each individual stressor, highlighting the vulnerability of homeothermic mammals under multiple environmental pressures, and opening new perspectives for ecotoxicology to consider not only the impacts of global warming, but also the deleterious effects of ELTs in interaction with emerging pollutants.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"111 ","pages":"Article 107547"},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879844","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":"Manganese induces neuroinflammation through SPON1-mediated activation of ERK1/2/NF-κB pathway","authors":"Fangfei Li ,&nbsp;Jie Zhang ,&nbsp;Xiaoli Ma ,&nbsp;Hao Chen ,&nbsp;Guiqiang Liang ,&nbsp;Yunfeng Zou","doi":"10.1016/j.ntt.2025.107543","DOIUrl":"10.1016/j.ntt.2025.107543","url":null,"abstract":"<div><div>Excessive accumulation of manganese (Mn) can cause neuroinflammation, impairing cognitive function. SPON1, a secreted glycoprotein in the extracellular matrix, is implicated in neuroinflammation, but its role in activating pro-inflammatory pathways in Mn-induced neuroinflammation remains unclear. This study employed <em>in vivo</em> and <em>in vitro</em> models to investigate Mn neuroinflammation. The expression levels of SPON1 and the ERK1/2/NF-κB pathway associated with inflammation were measured in male C57BL/6 mice after gavage of Mn at different doses (0, 25, 50, 100 mg/kg) for 12 weeks. SPON1 levels were measured after primary hippocampal neurons, primary cortical neurons, neuroblastoma cells (N2a), and microglial cells (BV2) were exposed to various concentrations of Mn for 24 h. We observed that <em>in vivo</em> Mn exposure significantly decreased SPON1 expression in the cortex but not in the hippocampus. Similarly, <em>in vitro</em> experiments demonstrated that Mn exposure significantly reduced SPON1 levels in primary cortical neurons, N2a, and BV2. In addition, Mn exposure increased the expression levels of ERK1/2 and NF-κB pathway proteins in the mouse cortex. Because BV2 cells are susceptible to inflammatory signals, they were chosen to elucidate how SPON1 induces neuroinflammation during Mn exposure. SPON1 knockdown increases the expression of inflammatory factors, whereas SPON1 overexpression inhibits the activation of the ERK1/2/NF-κB pathway and reduces inflammatory factor levels. In summary, these results suggest that Mn may affect the activation of ERK1/2/NF-κB pathway and the expression of inflammatory factors by inhibiting SPON1, ultimately promoting neuroinflammation.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"111 ","pages":"Article 107543"},"PeriodicalIF":2.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855826","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}