Neurotoxicology and teratology最新文献

{"title":"Bromelain mitigates monosodium glutamate-induced neurobehavioral impairment in mice by modulating AChE-MAO-GAD and oxido-inflammatory pathways: Experimental and computational insights","authors":"Joseph Chimezie ,&nbsp;Noah A. Omeiza ,&nbsp;Oludare M. Ogunyemi ,&nbsp;Abayomi M. Ajayi ,&nbsp;Jude I. Abeje ,&nbsp;Nafisat O. Abdullahi ,&nbsp;Grace O. Isehunwa ,&nbsp;Solomon Owumi ,&nbsp;Temitope G. Adedeji","doi":"10.1016/j.ntt.2026.107586","DOIUrl":"10.1016/j.ntt.2026.107586","url":null,"abstract":"<div><div>Excessive exposure to monosodium glutamate (MSG) induces glutamate-mediated excitotoxicity, oxidative stress, and neuroinflammation, culminating in neurobehavioral impairments. Bromelain, a cysteine protease derived from <em>Ananas comosus</em>, exhibits potent antioxidative and anti-inflammatory properties; however, its potential to attenuate excitotoxic neuronal injury remains insufficiently characterized. This study investigated the neuroprotective effects of bromelain against MSG-induced neurotoxicity through integrated behavioral, biochemical, histological, and computational analyses. Male Swiss mice (7–8 weeks) received MSG (4 g/kg, i.p.) to induce excitotoxicity and were subsequently treated orally with bromelain (50 or 100 mg/kg) or fluoxetine (1 mg/kg) for 21 days. Behavioral tests assessed locomotor, cognitive, and affective functions, while biochemical and histological analyses evaluated oxidative stress, neuroinflammatory markers, and neurotransmitter-modulating enzyme activities. In silico AlphaFold3 modeling and protein–protein docking were employed to elucidate bromelain's interactions with acetylcholinesterase (AChE), monoamine oxidase-B (MAO-B), and glutamate decarboxylase (GAD). Bromelain treatment significantly ameliorated MSG-induced behavioral deficits, restored cortical and hippocampal redox balance, suppressed pro-inflammatory cytokines, and preserved neuronal cytoarchitecture. It normalized neurotransmitter metabolism by inhibiting AChE and MAO-B activities while enhancing GAD function. AlphaFold3 modeling revealed a compact, high-confidence bromelain conformation (pLDDT &gt;90) with strong predicted binding affinities to catalytically active residues of AChE, MAO-B, and GAD, supporting its multi-target neuromodulatory role. Altogether, these findings provide the first integrated experimental and computational evidence that bromelain confers neuroprotection by regulating redox homeostasis, inflammation, and neurotransmitter signaling, highlighting its promise as a nutraceutical candidate for mitigating glutamate-mediated neurodegenerative disorders.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107586"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172212","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":"Profiles of polysubstance exposure in youth with fetal alcohol spectrum disorders and the association with neurodevelopmental outcomes","authors":"Madeline N. Delage ,&nbsp;Emily L. Speybroeck ,&nbsp;Alesia A. Richardson ,&nbsp;Lynn L. Cole ,&nbsp;Carson Kautz-Turnbull ,&nbsp;Christie L.M. Petrenko","doi":"10.1016/j.ntt.2026.107585","DOIUrl":"10.1016/j.ntt.2026.107585","url":null,"abstract":"<div><h3>Background</h3><div>Prenatal polysubstance exposure is highly prevalent among individuals with fetal alcohol spectrum disorders (FASD), yet little research has examined how specific patterns of co-exposure relate to neuropsychological outcomes. While alcohol is a known teratogen, other substances such as opioids, stimulants, cannabis, and nicotine also disrupt neurodevelopmental processes. Prior studies often assess single substances in isolation, failing to reflect real-world exposure patterns. Identifying meaningful patterns of co-occurring exposures and their associations with neuropsychological outcomes is critical for advancing targeted assessment and intervention.</div></div><div><h3>Methods</h3><div>Latent class analysis was conducted on data from 635 youth with FASD (mean age of diagnosis 7.4 years, range 0.24–21.61) to identify distinct profiles of prenatal exposure to six substances: alcohol, nicotine, marijuana, opioids, cocaine, and other drugs. Class differences in neuropsychological functioning, postnatal experiences, and demographics were examined using the Bolck, Croon, and Hagenaars method.</div></div><div><h3>Results</h3><div>A three-class solution demonstrated best model fit (AIC = 3945.216, saBIC = 3970.790, aLRT = 18.521, <em>p</em> = .006). Classes comprised of an all-exposure (Class 1, 47%), mainly alcohol exposed (Class 2, 46%), and mainly opioid exposed (Class 3, 7%). Significant between-class differences emerged across domains of memory, motor speed, sensory processing, and child-reported anxiety (χ² = 9.264–42.659, <em>p</em> = .046–0.001). Class 2 demonstrated significantly greater neuropsychological challenges, while Class 3 demonstrated high sensory sensitivity and anxiety. Results also reveal caregiver disruption was more prevalent in Class 2.</div></div><div><h3>Discussion</h3><div>Findings highlight heterogeneity in neuropsychological outcomes based on distinct patterns of prenatal polysubstance exposures. Neuropsychological assessment remains essential for capturing this variability and informing individualized, exposure-responsive care.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107585"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102581","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":"S-adenosyl-L-methionine reverses ethanol-induced developmental toxicity in FASD model of Danio rerio embryos via dual-modulation of oxidative stress and glutathione homeostasis","authors":"Prasanth Babu Nandagopal,&nbsp;Anu Varghese Kaithamattathil,&nbsp;Gopika Jayakrishnan,&nbsp;Sampath Raghul Kannan,&nbsp;Ramasamy Tamizhselvi,&nbsp;Venkatraman Manickam","doi":"10.1016/j.ntt.2026.107589","DOIUrl":"10.1016/j.ntt.2026.107589","url":null,"abstract":"<div><div>Fetal Alcohol Spectrum Disorder (FASD) represents a major global public health concern, affecting approximately 7.7 per 1000 births worldwide and remains as the most common preventable cause of lifelong neurodevelopmental impairment. Despite its prevalence, current clinical interventions are largely symptom-supportive and fail to address the underlying developmental pathology, underscoring the need for targeted, mechanism-based therapeutic strategies. Given the central involvement of oxidative stress and inflammation in FASD pathogenesis, this study evaluated the protective efficacy of S-adenosyl-L-methionine (SAMe), a key metabolic intermediate and universal methyl donor, using a zebrafish embryo model because of its high translational relevance and optical transparency. Fertilized embryos were exposed to 1.25% ethanol and co-treated with SAMe (15 and 30 μM) until 96 h post-fertilization (hpf). Ethanol exposure resulted in reduced survival and hatching rates, cardiac rhythm abnormalities, pronounced morphological defects, and compromised tissue integrity. SAMe treatment, particularly at 30 μM, significantly ameliorated these developmental abnormalities and associated biochemical dysregulations. Mechanistically, SAMe exerted a dual protective effect by restoring glutathione biosynthesis and attenuating oxidative stress-driven inflammatory responses. This was evidenced by marked reductions in reactive oxygen species, apoptosis, lipid peroxidation, and nitric oxide levels, alongside significant downregulation of pro-inflammatory cytokines, including <em>TNF-α</em> and <em>IL-1β</em>. Importantly, these biochemical and molecular improvements were consistently translated into phenotypic rescue, with substantial normalization of tissue architecture and developmental morphology. Collectively, these findings establish SAMe as a promising anti-teratogenic intervention that directly targets core oxidative and inflammatory pathways underlying FASD, highlighting its potential translational relevance as a mechanism-driven therapeutic strategy.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107589"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308481","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":"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}