Neurotoxicology最新文献

{"title":"Early postnatal exposure to permethrin and deltamethrin mixtures induces sex-specific hippocampal neurobehavioral and neurochemical alterations in adulthood","authors":"Sabrine Ben Slimene ,&nbsp;Khadija Boukholda ,&nbsp;Rahma Ammar ,&nbsp;Chloé Aman ,&nbsp;Anne-Emilie Allain ,&nbsp;Philippe De Deurwaerdère ,&nbsp;Ons Boudawara ,&nbsp;Abdeslam Chagraoui ,&nbsp;Michèle Bouchard ,&nbsp;Hamadi Fetoui","doi":"10.1016/j.neuro.2026.103468","DOIUrl":"10.1016/j.neuro.2026.103468","url":null,"abstract":"<div><div>Pyrethroid insecticides, including deltamethrin and permethrin, are known for their individual toxic effects; however, evidence regarding their combined toxicity during early developmental stages remains limited. The present study aimed to investigate the neurotoxic effects of co-exposure to deltamethrin and permethrin in lactating rats, focusing on emotional and cognitive behaviors, as well as cholinergic and monoaminergic neurotransmission in their progeny at adulthood (5 months of age). Dams were orally administered deltamethrin (1.35 mg/kg/day) and permethrin (34 mg/kg/day), either individually or in combination, from postnatal day (PND) 7 to PND 21. Our results demonstrated that co-exposure of lactating females to deltamethrin and permethrin induced behavioral alterations in their offspring, including impaired locomotor activity, anxiety-like behavior, and learning and memory deficits, with sex-specific effects. Furthermore, these toxicants triggered oxidative stress in the hippocampus, as indicated by elevated levels of malondialdehyde, nitric oxide, and advanced oxidation protein products, along with impaired enzymatic and non-enzymatic antioxidant defenses. Early postnatal exposure also caused sex-dependent modifications in monoamine concentrations across multiple brain regions. Mechanistically, molecular alterations of the cholinergic system were observed in the hippocampus of both male and female rats, as evidenced by downregulation of AChE, mAChR, and nAChR gene expression. These molecular changes were further confirmed by histological analyses. In conclusion, our findings demonstrate that exposure of lactating females to deltamethrin and permethrin, individually or in combination, induces sex-dependent, deleterious, and sometimes distinct neurodevelopmental effects in their offspring at PND 150.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103468"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diesel exhaust particles induce lasting and age-dependent damage to the brain in Drosophila melanogaster","authors":"Ranchana Yeewa ,&nbsp;Siwat Poompouang ,&nbsp;Kornravee Photichai ,&nbsp;Titaree Yamsri ,&nbsp;Natsinee U-on ,&nbsp;Wasinee Wongkummool ,&nbsp;Phatsara Manussabhorn ,&nbsp;Luca Lo Piccolo ,&nbsp;Salinee Jantrapirom","doi":"10.1016/j.neuro.2026.103464","DOIUrl":"10.1016/j.neuro.2026.103464","url":null,"abstract":"<div><div>Diesel exhaust particles (DEP), major air pollutants emitted from automobile engines, contain numerous toxic compounds. Although the adverse effects of DEP exposure on the respiratory and cardiovascular systems are well documented, its impact on brain health remains poorly understood. In this study, <em>Drosophila melanogaster</em> was used as a model organism to investigate the neurological effects of DEP exposure and the impact of exposure cessation across different age groups. Molecular, histopathological, and behavioral markers were assessed before and after exposure to varying DEP doses at different time intervals. DEP exposure induced age-dependent cellular responses in the brain, including elevated reactive oxygen species (ROS), increased neuroinflammation, and disruption of the blood-brain barrier (BBB). Prolonged exposure led to pronounced vacuolization in the brains of aged flies. Cessation of DEP exposure resulted in partial recovery in young flies, particularly when implemented early in life, whereas aged flies showed limited benefit, with persistent signs of likely irreversible brain damage. Overall, this findings support the need for greater public awareness and careful consideration in public health policies to limit long-term DEP exposure, especially among older individuals, and to promote strategies that reduce potential risks to brain health associated with air pollution.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"114 ","pages":"Article 103464"},"PeriodicalIF":3.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869057","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":"Targeting glutamate receptors with IEM-1925: A strategy against soman-induced status epilepticus and neurodegeneration","authors":"Yuxin Lin,&nbsp;Qian Jin,&nbsp;Yuanqing Chen,&nbsp;Jingyan Wang,&nbsp;Yi Zhang,&nbsp;Manzhu Cao,&nbsp;Jingjing Shi,&nbsp;Liqin Li","doi":"10.1016/j.neuro.2026.103389","DOIUrl":"10.1016/j.neuro.2026.103389","url":null,"abstract":"<div><div>Exposure to organophosphorus nerve agents (OPNAs) like soman frequently develops status epilepticus (SE), leading to brain damage. Existing antiseizure medications (e.g., diazepam, DZP) often demonstrate insufficient efficacy. To develop more effective treatments for OPNA-induced seizures, this study evaluated the efficacy of glutamate receptor antagonists with distinct mechanisms of action in a soman-induced rat seizure model. After 5 min of subcutaneous exposure to 110 μg/kg soman, which induced SE, rats received intraperitoneal injections (10 mg/kg) of perampanel (PER), fanapanel (FNP), IEM-1925 (IEM), or DZP. The results showed that IEM significantly suppressed seizure activity and improved survival. The survival rate of the vehicle-treated control group was 31.25 %, whereas DZP, FNP, and IEM increased survival rates to 50 %, 43.75 %, and 56.25 % respectively. Electroencephalographic (EEG) recordings for 24 h indicated that both DZP and IEM controlled soman-induced SE. However, while DZP initially blocked the onset of seizures, they recurred after its transient anticonvulsant effect wore off. In contrast, IEM reduced behavioral convulsion intensity and total duration of SE. Histopathological examinations (HE, Nissl, immunohistochemistry, and immunofluorescence) showed that IEM attenuated hippocampal CA1, CA2, and DG neuronal damage. Behavioral tests (open field, novel object recognition, and Y maze) confirmed IEM outperformed DZP and the solvent-treated group in ameliorating soman-induced anxiety, cognitive dysfunction, and memory impairment. In conclusion, IEM demonstrates potent triple effects-antiseizure, neuroprotective, and cognitive improving in soman exposure model, providing a novel therapeutic strategy and candidate drug for the medical treatment of OPNAs poisoning.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103389"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952523","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":"Larval zebrafish as a translational model for neurotoxicity screening of emerging psychoactive substances","authors":"Courtney Hillman ,&nbsp;James Kearn ,&nbsp;Maciej Trznadel ,&nbsp;Matthew J. Winter ,&nbsp;Matthew O. Parker","doi":"10.1016/j.neuro.2026.103386","DOIUrl":"10.1016/j.neuro.2026.103386","url":null,"abstract":"<div><div>The rapid emergence of novel psychoactive substances poses a growing neurotoxicological concern, characterised by poorly defined mechanisms, high potency, and escalating overdose fatalities. Effective treatments remain limited, highlighting the need for scalable <em>in vivo</em> systems capable of identifying hazardous pharmacological profiles before widespread harm occurs. Here, we evaluated larval zebrafish (<em>Danio rerio</em>) as a medium/high-throughput model for early hazard assessment of γ-aminobutyric acid (GABA)_A positive allosteric modulators (PAMs) and N-methyl-<span>D</span>-aspartate (NMDA) receptor antagonists. Behavioural analysis of 4 days post-fertilisation (dpf) larvae revealed concentration-dependent locomotor effects consistent with mammalian pharmacodynamics, while whole-body bioanalysis confirmed compound uptake, revealing substance-specific differences in internal exposure. Notably, diazepam and tiletamine deviated from expected class profiles, highlighting the model’s sensitivity to compounds with distinctive neuropharmacological signatures. These findings demonstrate the translational value of larval zebrafish for rapid neurotoxicity screening and pharmacodynamic profiling, offering an ethically advantageous, 3Rs-aligned platform to inform overdose treatment development and prioritisation of emerging psychoactive threats.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103386"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903965","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":"Triggers of highly lethal seizures induced by novel stimulants: A systematic review focused on synthetic cathinones and phenethylamines","authors":"Martin Macháček ,&nbsp;Markéta Bébarová","doi":"10.1016/j.neuro.2026.103391","DOIUrl":"10.1016/j.neuro.2026.103391","url":null,"abstract":"<div><div>Synthetic cathinones and phenethylamines are increasingly prevalent novel psychoactive substances with stimulant and hallucinogenic properties. They are associated with acute symptomatic seizures, often with lethal outcomes. Current management is usually limited to symptomatic therapy, as serotonin and sympathomimetic toxidromes are widely regarded as the main seizure-inducing mechanisms. However, intoxications frequently involve severe organ toxicities or metabolic disturbances with high epileptogenic potential, which may be preventable or treatable. This review aimed to assess seizure mechanisms beyond central monoaminergic toxicity to identify additional factors and improve seizure management. A systematic search of PubMed and Web of Science (2003–2024) identified reports describing individual human cases of acute intoxication with synthetic cathinones or phenethylamines, published in English and providing detailed clinical data. Inclusion criteria were met by 42 cases from 34 reports. A descriptive synthesis was performed to summarize observed patterns across substance groups. Most seizures occurred in previously healthy young adults and resulted in death in nearly 50 % of cases, with higher fatality among cathinone users. Serotonin and sympathomimetic toxidromes were present in most cases, supporting a primary role in seizure generation. However, intracranial hemorrhage and cerebral edema (often precipitated by hypertensive crisis), hypoglycemia, and hyponatremia likely contributed to seizures in several cases. Based on these findings, we recommend that young adults presenting with seizures and signs of monoaminergic toxicity, in whom synthetic cathinone or phenethylamine intoxication is confirmed or suspected, should be promptly assessed for focal brain injury and metabolic disturbances to identify treatable causes and potentially improve outcomes.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103391"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980113","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":"Neuroprotection via IGF-1 neuronal signaling activation by melatonin and edaravone synergy in methylmercury-induced ALS-like neurotoxicity: Comprehensive analysis of brain regions, spinal cord, CSF, and blood plasma","authors":"Gurudev Singh Raina ,&nbsp;Sidharth Mehan ,&nbsp;Ghanshyam Das Gupta","doi":"10.1016/j.neuro.2026.103398","DOIUrl":"10.1016/j.neuro.2026.103398","url":null,"abstract":"<div><div>Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration, oxidative stress, neuroinflammation, and neurotransmitter imbalances. This study explored the neuroprotective potential of melatonin (MLT), alone and in combination with edaravone (EDR), in a methylmercury (MEME)-induced ALS rat model. MEME exposure effectively replicated ALS pathology, causing behavioral deficits, oxidative stress, neuroinflammation, apoptosis, and widespread structural damage in critical brain regions and the spinal cord. MLT administration at 5 mg/kg (MLT5) and 10 mg/kg (MLT10) significantly mitigated MEME-induced neurotoxicity in a dose-dependent manner. MLT improved motor function, reduced depressive-like behavior, and restored body weight. Biochemically, MLT enhanced antioxidant defenses, including superoxide dismutase (SOD) and catalase (CAT), reduced pro-inflammatory cytokines, interleukin-1 beta (IL-1β), increased anti-inflammatory cytokines, interleukin-10 (IL-10), and restored neurotransmitter balance like dopamine and Gamma-Aminobutyric Acid (GABA). Mechanistically, MLT activated the IGF-1 signaling pathway, promoting neuronal survival and reducing apoptosis (Caspase-3 expression). Histopathological analyses confirmed that MLT preserved neuronal and glial integrity, reduced demyelination, and restored myelin basic protein (MBP) levels in brain and cerebrospinal fluid. The combination of MLT and EDR exhibited synergistic neuroprotective effects, surpassing the efficacy of individual treatments in reducing oxidative stress, inflammation, and neuronal damage. Behavioral and biochemical improvements were paralleled by systemic recovery, as evidenced by normalized hematological parameters and reduced methylmercury accumulation in brain tissues. These findings underscore MLT, particularly in combination with EDR, as a potent therapeutic agent for ALS, offering multi-targeted neuroprotection. Future studies should explore its translational potential in clinical settings for the treatment of neurodegenerative diseases.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103398"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132350","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":"Beta-caryophyllene restores liver–brain axis integrity in thioacetamide-induced hepatic encephalopathy: Behavioral and molecular insights","authors":"Samet Tekin ,&nbsp;Merve Bolat ,&nbsp;İsmail Bolat ,&nbsp;Ömercan Alat ,&nbsp;Burak Batuhan Laçin ,&nbsp;Burak Çınar ,&nbsp;Aslıhan Atasever ,&nbsp;Mehmet Emin Kanat ,&nbsp;Emin Şengül ,&nbsp;Mohamad Warda ,&nbsp;Ahmet Hacımüftüoğlu","doi":"10.1016/j.neuro.2026.103400","DOIUrl":"10.1016/j.neuro.2026.103400","url":null,"abstract":"<div><div>Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver dysfunction, driven by hyperammonemia, oxidative stress, neuroinflammation, apoptosis, and endoplasmic reticulum (ER) stress, which disrupt the hepato-encephalic axis and impair cognition and motor functions. Despite its clinical burden, effective therapies that target this multi-organ pathology remain limited. β-Caryophyllene (BCP), an antioxidant and anti-inflammatory dietary sesquiterpene, has not been evaluated for its ability to modulate liver–brain crosstalk in HE. This study investigated the hepatoprotective and neuroprotective effects of BCP in a rat model of thioacetamide (TAA)-induced HE. Rats received TAA (200 mg/kg, i.p.) for three days, followed by BCP (100–400 mg/kg) for 14 days. A comprehensive evaluation included serum biochemistry, oxidative stress indices, inflammatory cytokines, apoptosis-related proteins, neurotrophic factors (BDNF), astroglial activation marker (GFAP), ER stress regulators (GRP78, IRE1, XBP1, PERK, CHOP, ATF6), histopathology, and behavioral outcomes. TAA caused severe hepatic and cerebral injury with elevated liver enzymes, oxidative and inflammatory mediators, ER stress dysregulation, pro-apoptotic signaling, reduced BDNF and GFAP, and impaired motor and exploratory behaviors. BCP treatment dose-dependently restored biochemical and molecular parameters, suppressed oxidative stress and neuroinflammation, normalized ER stress signaling, promoted anti-apoptotic pathways, preserved BDNF and maintained astroglial status as reflected by GFAP, and improved histoarchitecture. Importantly, moderate to high doses fully restored locomotor and exploratory activity, indicating coordinated protection across the hepato-encephalic axis. Here, for the first time, the BCP concurrently mitigates hepatic and cerebral pathology via oxidative, inflammatory, apoptotic, and ER stress pathways, supporting its translational potential as a dual hepatoprotective and neuroprotective candidate for xenobiotic-induced HE and related liver–brain disorders.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103400"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137790","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":"Synthetic cannabidiol analogues exhibit lower toxicity than cannabidiol and protect against ethanol-induced apoptosis in SH-SY5Y cells","authors":"Carolina Aparecida Faria Almeida ,&nbsp;Gabriela Salles ,&nbsp;Vitor Bruno ,&nbsp;Jessyca Milene Ribeiro ,&nbsp;Alessandra Oliveira Silva ,&nbsp;Giulia de Assis Braz ,&nbsp;Felype Valentim Duarte Castelhano ,&nbsp;Graziella dos Reis Rosa Franco ,&nbsp;Cláudio Viegas Jr. ,&nbsp;Tania Marcourakis ,&nbsp;Larissa Helena Lobo Torres ,&nbsp;Raphael Caio Tamborelli Garcia","doi":"10.1016/j.neuro.2026.103411","DOIUrl":"10.1016/j.neuro.2026.103411","url":null,"abstract":"<div><div>Cannabidiol (CBD) shows therapeutic potential for treating alcohol use disorder (AUD); however, its neurotoxicological profile remains insufficiently characterized, especially when compared with emerging synthetic analogues designed to improve safety. This study compares the neurotoxic and mechanistic profiles of CBD and two synthetic derivatives, PQM-242 and PQM-249, and evaluates their ability to attenuate ethanol-induced cellular injury. Human SH-SY5Y neuroblastoma cells were exposed to increasing concentrations (0.1–1000 µM) to generate concentration-response curves, estimate no-observed-adverse-effect levels (NOAELs), and determine cytotoxicity thresholds. Cell viability (MTT), apoptosis (annexin V/propidium iodide), and Bax and Bcl-2 expression (western blot) were assessed after 48 h of exposure. CBD showed an LC50 of 44 µM, whereas PQM-242 and PQM-249 displayed LC50 values &gt; 600 µM, indicating markedly lower intrinsic toxicity in the proposed study model. The NOAELs for PQM-242 and PQM-249 were 100 µM, compared with 10 µM for CBD. For co-exposure studies, 10 µM was selected to enable direct comparison under ethanol challenge (250 mM). All compounds reduced ethanol-induced loss of viability and apoptosis, and PQM-242 additionally prevented ethanol-mediated Bax upregulation. Overall, PQM-242 and PQM-249 demonstrated enhanced cellular safety and maintained protective activity, supporting their further investigation as candidate molecules for AUD.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103411"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220282","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":"Prolonged duration induces divergent transcriptomic responses to manganese, distinct from concentration effects, in an SH-SY5Y neurotoxicity model","authors":"Xueqi Tang ,&nbsp;Priyanka Baloni ,&nbsp;Michael Aschner ,&nbsp;Aaron B. Bowman","doi":"10.1016/j.neuro.2026.103393","DOIUrl":"10.1016/j.neuro.2026.103393","url":null,"abstract":"<div><div>Understanding manganese (Mn) neurotoxicity requires experimental models that realistically reflect human exposure scenarios. A key limitation of current <em>in vitro</em> paradigms is the reliance on acute, high-concentration exposures, which may not accurately capture the molecular consequences of long-term Mn accumulation. To address this, this study compared transcriptomic responses to acute (6-hour) and chronic (40-day) Mn exposures in SH-SY5Y cells, using Mn concentrations spanning near-physiological to sub-cytotoxic ranges. The 6-hour exposure design replicates a widely applied acute duration in the literature, while the 40-day duration was selected to mimic prolonged, low-level Mn burden reported in epidemiological and occupational studies. Bulk RNA sequencing revealed that chronic Mn exposure induced distinct and more extensive transcriptional alterations compared to acute exposure, independent of concentration. Pathway enrichment analyses indicated that cellular functions selectively perturbed under chronic conditions are highly relevant to neurodegenerative risks and aligns with independent Parkinson’s disease transcriptomic datasets. These pathways include axonal guidance signaling, amyloid fiber formation, extracellular matrix organization, and synaptic functioning. In contrast, acute exposures primarily disturbed intracellular ion homeostasis maintenance mechanisms. Protein kinase A signaling and metallothionein-mediated metal-binding pathway were the only two pathways that were shared between both applied durations exposed at Mn concentrations with reported adverse outcomes. Transcriptomic alterations in this study highlighted the contribution of mechanisms related to normal Mn-dependent cellular functions in the development of its neurotoxicity. Furthermore, these results emphasized that exposure duration is a critical determinant to be considered when evaluating long-term Mn overload-induced neurodegeneration via <em>in vitro</em> platforms.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103393"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053289","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":"From clinical observation to experimental validation: Investigating the neurotoxic impact of dimethylacetamide","authors":"Hizir Asliyuksek ,&nbsp;Nihan Hande Akcakaya ,&nbsp;Rumeysa Hekimoglu ,&nbsp;Simay Bozkurt ,&nbsp;Berna Yeniceri ,&nbsp;Onder Huseyinbas ,&nbsp;Sibel Atacan ,&nbsp;Mukaddes Esrefoglu ,&nbsp;Emrah Yucesan ,&nbsp;Beyza Goncu","doi":"10.1016/j.neuro.2026.103392","DOIUrl":"10.1016/j.neuro.2026.103392","url":null,"abstract":"<div><div>Dimethylacetamide (DMAC) is a polar organic solvent widely used in the production of synthetic fibers and other industrial applications. Its hepatotoxic potential has been well documented in laboratory animals and occupationally exposed workers, establishing DMAC as a recognized industrial hazard. However, evidence regarding its neurological effects remains scarce. We report a clinical case of accidental DMAC inhalation associated with diffuse cortical hyperintensity on brain magnetic resonance imaging, raising concern for direct neurotoxicity. To address this knowledge gap, we investigated the neurotoxic potential of DMAC in a controlled rat model experiment. Animals subjected to repeated intraperitoneal DMAC administration exhibited cortical and subcortical histopathological alterations consistent with neurotoxicity, accompanied by significant hepatic and renal injury. These findings provide the first experimental evidence that DMAC toxicity extends beyond hepatotoxicity to involve the central nervous system and kidneys, highlighting its potential for multi-organ toxicity and reinforcing concerns regarding occupational exposure risks.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103392"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046827","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}