Neurotoxicology and teratology最新文献

{"title":"Gene × environment interaction between latrophilin-3 (Lphn3 or Adgrl3) and developmental permethrin exposure in Sprague Dawley rats","authors":"Charles V. Vorhees,&nbsp;Adam L. Fritz,&nbsp;Brooke M. Gollaway,&nbsp;Michael T. Williams","doi":"10.1016/j.ntt.2026.107587","DOIUrl":"10.1016/j.ntt.2026.107587","url":null,"abstract":"<div><div>Attention deficit hyperactivity disorder (ADHD) occurs in 9.8% of U.S. children and has a large hereditary component arising from multiple gene variants. One of these is <em>Latrophiln-3</em> (<em>LPHN-3</em>). Using CRISPR/Cas9 we deleted exon 3 in Sprague Dawley rats to create a global <em>Lphn3</em> knockout (gKO). The gKO rats are hyperactive, startle hyper-reactive, impulsive, and have impaired working, spatial, and egocentric learning and memory. Permethrin (PRM) is a widely used pyrethroid insecticide. Acute exposure to PRM alters acoustic startle but its long-term effects from developmental exposure are unknown. The present experiment tested whether <em>Lphn3</em> heterozygosity interacts with PRM developmental exposure to affect post exposure neurobehavior in rats. We used Lphn3^+/− (Het) rats since they have an intermediate phenotype compared with gKO rats that are severely affected (<span><span>Regan et al., 2022</span></span>). There were 4 groups: Lphn3-Het + PRM (120 mg/kg daily by gavage from postnatal day (P) 6–20 in 5 mL/kg corn oil (CO)), Lphn3-Het + CO, wildtype (WT) + PRM, and WT + CO. From 25 litters, 20–22 males and 20–22 females of each combination were obtained with not more than one male and one female from any given litter. Adult offspring were tested in an automated open-field for 1 h, in home-cage activity for 72 h, startle (including prepulse inhibition), novel object recognition (NOR), working memory (radial water maze (RWM)), spatial learning (Morris water maze (MWM)), and egocentric learning in the Cincinnati water maze (CWM). On acquisition and reversal probe trials in the MWM and on learning trials in the CWM, Lphn3-Het-PRM rats performed worse than other groups. In open-field, home-cage, startle, NOR, and RWM there were no interactions between <em>Lphn3</em> and PRM but there were effects of Lphn3 heterozygosity. The results indicate that heterozygosity of the ADHD risk gene <em>Lphn3</em> when combined with developmental exposure to PRM increases the adverse effects of either one alone.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107587"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776511","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":"Mechanistic links between cadmium and MAPK pathways leading to neurodegeneration","authors":"Sneha De ,&nbsp;Shinjini Kanrar ,&nbsp;Aluru Parithathvi ,&nbsp;P. Harshitha ,&nbsp;Herman Sunil Dsouza","doi":"10.1016/j.ntt.2026.107588","DOIUrl":"10.1016/j.ntt.2026.107588","url":null,"abstract":"<div><div>Cadmium, a Group 1 carcinogen, represents a significant public health concern due to its widespread environmental distribution and exposure through industrial processes, contaminated water, dietary intake, and tobacco use. Prolonged cadmium exposure is associated with systemic toxicity, including neurodegenerative outcomes mediated by oxidative stress, protein misfolding, neuroinflammation, and mitochondrial dysfunction. Disruption of autophagy and MAPK signalling pathways (ERK, JNK, and P38) further impairs neuronal function. Cadmium-induced misfolding of key proteins such as tau, amyloid-β, and α-synuclein is implicated in Alzheimer's and Parkinson's diseases. This systematic review aims to map the role of cadmium exposure in neurodegenerative disorders, with a focus on oxidative stress, protein misfolding, autophagy dysregulation, and MAPK signalling pathways. A thorough literature search was conducted across databases including PubMed, Scopus, and Science Direct using specific keywords. Elevated markers, including IL-6, IL-8, and cytochrome <em>c</em>, may serve as diagnostic indicators of cadmium-associated neurodegeneration.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107588"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271290","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":"Neuroprogramming of prenatal phthalate exposures on fluid cognition: A latent variable modeling approach to quantify exposure burden and integrate neurobehavioral data","authors":"Jamil M. Lane ,&nbsp;Nathan Cohen ,&nbsp;Vishal Midya ,&nbsp;Cecilia S. Alcala ,&nbsp;Shoshannah Eggers ,&nbsp;Sandra Martinez-Medina ,&nbsp;Damaskini Valvi ,&nbsp;Martha M. Téllez-Rojo ,&nbsp;Deborah A. Cory-Slechta ,&nbsp;Robert O. Wright ,&nbsp;Shelley H. Liu","doi":"10.1016/j.ntt.2025.107575","DOIUrl":"10.1016/j.ntt.2025.107575","url":null,"abstract":"<div><h3>Background</h3><div>Phthalates are endocrine-disrupting chemicals with neuroactive properties linked to maladaptive neurodevelopment in children. However, few studies have utilized latent variable methodologies to estimate their cumulative impact and assess the complex integration of cognitive processes that characterize fluid cognition—the ability to efficiently process, manipulate, and integrate information to solve reasoning problems.</div></div><div><h3>Objective</h3><div>We investigated the prenatal trimester-specific neuroprogramming effects of the phthalate burden scores on fluid cognition in Mexican children.</div></div><div><h3>Methods</h3><div>Children (<em>n</em> = 626) aged 6–7 years from a prospective pregnancy cohort in Mexico City were administered subtests from the CANTAB, completing the between error, strategy, and mean latency measures intended to evaluate a broad spectrum of cognitive domains representative of fluid cognition. Phthalate metabolites were measured in maternal urine collected at 2nd and 3rd pregnancy trimesters. A CFA validated and quantified two correlated latent phthalate burden scores representing prenatal exposure to low molecular weight (LMW) and high molecular weight (HMW) phthalates. Trimester-specific models using a covariate-adjusted SEM estimated the associations of latent phthalate burden scores with a latent construct of fluid cognition, an integration of working memory, executive function, and attention tasks.</div></div><div><h3>Results</h3><div>In the 3rd trimester, higher LMW phthalate burden was associated with poorer fluid cognition (b = −1.860; [95 % CI = −3.505, −0.215]; <em>p</em> = 0.027), while HMW phthalate burden showed a positive association (b = 1.815; [95 % CI = 0.176, 3.453]; <em>p</em> = 0.030). Conversely, in the 2nd trimester, neither burden levels of LMW (b = −0.508; [95 % CI = −1.639, 0.623]; <em>p</em> = 0.378) nor HMW (b = 0.451; [95 % CI = −0.671, 1.573]; <em>p</em> = 0.431]; <em>p</em> = 0.44) phthalate demonstrated significant associations with fluid cognitive performance.</div></div><div><h3>Conclusion</h3><div>The temporal sensitivity of prenatal phthalate exposures on fluid cognition showed effects in later stages, with higher LMW burden linked to poorer performance and HMW burden showing a positive association. Our findings emphasize latent variable approaches and the need for more research on exposure-driven integrated cognitive programming.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"113 ","pages":"Article 107575"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692907","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 early childhood air pollution exposure and neurodevelopmental outcomes in early childhood","authors":"Christina Berninger ,&nbsp;Yingying Xu ,&nbsp;Patrick Ryan ,&nbsp;Kim M. Cecil ,&nbsp;Bruce P. Lanphear ,&nbsp;Aimée Vester ,&nbsp;Kimberly Yolton","doi":"10.1016/j.ntt.2025.107576","DOIUrl":"10.1016/j.ntt.2025.107576","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to ambient air pollution, including fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and elemental carbon, has been associated with worse neurodevelopmental outcomes in children, but research on early childhood outcomes is limited.</div></div><div><h3>Objective</h3><div>This study examined the associations between gestational and early childhood exposures to PM_2.5 and NO₂ and child developmental outcomes measured at ages 1, 2, and 3 years.</div></div><div><h3>Methods</h3><div>In the Health Outcomes and Measures of the Environment (HOME) Study, a longitudinal pregnancy and birth cohort, we used spatiotemporal models to estimate the concentration of each air pollutant at participants' home addresses during early brain development. Neurodevelopmental outcomes were measured using the Bayley Scales of Infant Development, Second Edition (BSID-II) at ages 1, 2, and 3 years. For 329 children, we examined the associations of air pollution with BSID-II scores using generalized linear models with generalized estimating equations (GEE).</div></div><div><h3>Results</h3><div>Gestational and early childhood NO₂ concentrations were positively associated with cognitive development at age 1 year but negatively associated with cognitive development at age 3 years. Similarly, PM_2.5 exposure through age 3 years was negatively associated with cognitive development at age 3 years. Gestational NO₂ concentration was positively associated with motor development at age 1 year but negatively associated with motor development at ages 2 and 3 years.</div></div><div><h3>Discussion</h3><div>These results suggest that exposure to traffic-related air pollution during gestation and after birth may impact neurodevelopment in early childhood.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"113 ","pages":"Article 107576"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768670","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":"Environmental factors associated with microcephaly in Africa: A systematic review","authors":"Pelagie Izabayo ,&nbsp;Jean Claude Hakizimana ,&nbsp;Annette Uwineza ,&nbsp;Abdullateef Isiaka Alagbonsi","doi":"10.1016/j.ntt.2025.107577","DOIUrl":"10.1016/j.ntt.2025.107577","url":null,"abstract":"<div><h3>Introduction</h3><div>Microcephaly, a condition characterized by a head circumference below the mean for age and sex, is a significant indicator of impaired fetal brain development. While some environmental factors have been associated with the development of microcephaly in Africa, the available information remains disjointed, making it difficult for healthcare providers and policy makers to translate the information to preventive measures in maternal and child health. This systematic review aims to synthesize primary studies on environmental determinants of microcephaly, focusing on African populations.</div></div><div><h3>Method</h3><div>A systematic literature search was conducted using PubMed, Scopus, AJOL, and Wiley Online Library to identify studies published between 2000 and 2025, focusing on environmental exposures and microcephaly in neonates and infants. Observational and interventional studies in English were included, following PRISMA 2020 guidelines. Data were extracted and tabulated by country, exposure type, study design, and reported outcomes.</div></div><div><h3>Results</h3><div>Sixteen African studies found a multifactorial relationship between environmental exposures and microcephaly. Zika virus infection was a consistent contributor, with maternal febrile illnesses, inadequate antenatal care, HIV exposure, and heavy metal toxicity also linked. Pesticide exposure, particularly to organophosphates and DDT, was associated with neurodevelopmental delays and restricted cranial growth. Ambient air pollution was negatively correlated with neonatal head circumference. Socioeconomic vulnerabilities intensified these environmental risks, especially during epidemic crises like Zika virus outbreaks.</div></div><div><h3>Conclusion</h3><div>Microcephaly in African populations is a multifactorial issue, influenced by emerging infections like ZIKV, chronic environmental exposures, and healthcare gaps. It calls for integrated public health strategies, including surveillance, early prenatal screening, environmental regulation, and region-specific diagnostic standards. Global evidence supports shared biological vulnerability in low-resource settings.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"113 ","pages":"Article 107577"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794306","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":"Is there a glymphatic pathway to environmental risk in neurodevelopmental disorders?","authors":"Maiara de Aguiar da Costa ,&nbsp;Sofia Januário Bolan ,&nbsp;Maria Fernanda Pedro Ebs ,&nbsp;Simone Lespinasse Araújo ,&nbsp;Cristiano Juliano Faller ,&nbsp;Tatiana Barichello ,&nbsp;Michael Aschner ,&nbsp;Jaqueline da Silva Generoso ,&nbsp;Cinara Ludvig Gonçalves","doi":"10.1016/j.ntt.2025.107578","DOIUrl":"10.1016/j.ntt.2025.107578","url":null,"abstract":"<div><div>The glymphatic system (GS) is a glia-dependent perivascular network that mediates cerebrospinal fluid-interstitial fluid exchange and facilitates the clearance of neurometabolites. GS transport is sleep-dependent, with waste elimination heightened during non-rapid eye movement sleep. Emerging evidence links GS dysfunction with neurodevelopmental disorders (NDDs), including autism spectrum disorder, schizophrenia, and attention-deficit/hyperactivity disorder, disorders that frequently co-occur with sleep disturbances. In parallel, multiple environmental toxicants have been associated with adverse neurodevelopment. This study aims to integrate current evidence on the interplay between toxicants, GS dysfunction, and NDDs, highlighting shared biological pathways and exploring potential therapeutic targets. Evidence gaps include the absence of studies directly investigating toxicant effects on GS within NDDs populations, limited longitudinal data across sensitive developmental windows, scarce integration of GS-sensitive imaging, cerebrospinal fuid (CSF) biomarkers, and underassessment of sex differences and exposure mixtures. Translational opportunities span sleep optimization and GS-targeted strategies (e.g., enhancing CSF transport); among pharmacologic candidates, the α2-adrenergic agonist dexmedetomidine shows sedative–anxiolytic, anti-inflammatory, and neuroprotective signals warranting investigation. This narrative review synthesizes current evidence and delineates priorities to test the exposome–glymphatic–neurodevelopment axis.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"113 ","pages":"Article 107578"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sevoflurane induced hippocampal neuron cell injury via the miR-132-5p/BDNF axis and further caused cognitive impairment in rats","authors":"Junbo Peng ,&nbsp;Xiaoxiao Dai ,&nbsp;Guohai Chu","doi":"10.1016/j.ntt.2025.107567","DOIUrl":"10.1016/j.ntt.2025.107567","url":null,"abstract":"<div><h3>Background</h3><div>Sevoflurane (Sevo) could cause cognitive dysfunction in patients. MiR-132-5p is associated with nervous system functions. Therefore, this study explored the role of miR-132-5p in Sevo-induced cognitive impairment. This study aimed to provide useful information on preventing Sevo-induced cognitive impairment.</div></div><div><h3>Methods</h3><div>Sprague-Dawley rats and HT22 cells were involved in this study. A Sevo-treated rat model was constructed by making the rat inhale 2 % Sevo for 5 h. A Morris water maze (MWM) assay was conducted to assess the cognitive ability of rats. The qRT-PCR was used to measure miRNA and gene expression. Western Blot was used to measure protein expression. The oxidative stress status was measured using antioxidant activity assay. The flow cytometry was applied for the cell apoptosis assay. The mechanism was investigated using dual luciferase reporter assay.</div></div><div><h3>Results</h3><div>Sevo impaired the cognitive function of rats. Sevo-treatment upregulated miR-132-5p in rat hippocampal tissues, and miR-132-5p further downregulated BDNF. MiR-132-5p mediated the effect of Sevo on rat cognitive functions. MiR-132-5p affected rat cognitive functions by downregulating BDNF. In hippocampal neuron cells, Sevo-treatment upregulated miR-132-5p, and miR-132-5p downregulated BDNF. MiR-132-5p mediated the disrupting effect of Sevo on hippocampal neuron cells. MiR-132-5p caused hippocampal neuron cell damage by downregulating BDNF.</div></div><div><h3>Conclusion</h3><div>Sevo could induce rat cognitive impairments. Sevo-treatment upregulated miR-132-5p and miR-132-5p could downregulate BDNF expression in hippocampal tissues and neuron cells. MiR-132-5p mediated the disrupting effect of Sevo on hippocampal neuron cells and cognitive functions. MiR-132-5p caused hippocampal neuron cell injury and cognitive dysfunction by downregulating BDNF.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"112 ","pages":"Article 107567"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145391693","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":"2025-11-01","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":"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":"2025-11-01","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":"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":"2025-11-01","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}