Neurotoxicology最新文献

{"title":"Protective role of isobenzofuran-1(3H)-one derivative against neuronal injury and enzyme activity dysregulation induced by bipyridyl herbicide in adult male rats","authors":"Iára Mariana Léllis Ribeiro ,&nbsp;Ana Luiza Sciandretti Albuquerque ,&nbsp;Lucas Gabriel Vieira ,&nbsp;Laser Antonio Machado Oliveira ,&nbsp;Frank Silva Bezerra ,&nbsp;Róbson Ricardo Teixeira ,&nbsp;Rodrigo Cunha Alvim de Menezes ,&nbsp;Katiane de Oliveira Pinto Coelho Nogueira","doi":"10.1016/j.neuro.2025.05.002","DOIUrl":"10.1016/j.neuro.2025.05.002","url":null,"abstract":"<div><div>Diquat (DQT) is a bipyridyl herbicide widely used in agriculture. The exposure to DQT may overwhelm the antioxidant system, leading to oxidative damage in organs such as the brain, liver, and kidneys. The brain is particularly susceptible to oxidative damage because of its high oxygen consumption, relatively low antioxidant levels, and limited regenerative capacity. Faced with stressful agents, using compounds capable of repairing and replacing oxidized biomolecules is a promising option to maintain redox homeostasis. Isobenzofuran-1 (3H)-one derivative (named compound 1) emerges as a potential candidate to control the redox imbalance induced by DQT in the brain. The present study aimed to explore the neurotoxicity mechanisms of DQT and the antioxidant potential of compound 1 within the hippocampus and cortex, brain regions impacted by AD, using in vitro and in vivo models. Treatment with compound 1 reduced intracellular levels of ROS and lipid peroxidation in primary cultures of hippocampal neurons caused by DQT. Moreover, compound 1 significantly elevated GSH levels in the brains of rats subjected to DQT treatment. Treatment with compound 1 also decreased lipid peroxidation and carbonylated protein levels in the brain induced by DQT. The exposure to DQT resulted in neuronal injury in the hippocampus. Compound 1, protected against neuronal damage in CA1 and dentate gyrus hippocampal regions. The findings of our study suggest that DQT leads to oxidative damage and neuronal death in both the hippocampus and the cortex. Furthermore, compound 1 exhibits neuroprotective qualities by reducing oxidative damage caused by exposure to DQT.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 368-376"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950542","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":"Pharmacological effects and pharmacokinetics of the novel synthetic cathinone α-pyrrolidinoisohexanophenone (α-PiHP) compared with α-pyrrolidinovalerophenone (α-PVP) in mice","authors":"Anne Marte Baarset ,&nbsp;Synne Steinsland ,&nbsp;Elisabeth Nerem ,&nbsp;Jannike Mørch Andersen ,&nbsp;Michael H. Baumann ,&nbsp;Inger Lise Bogen","doi":"10.1016/j.neuro.2025.05.005","DOIUrl":"10.1016/j.neuro.2025.05.005","url":null,"abstract":"<div><div>α-Pyrrolidinoisohexanophenone (α-PiHP) is a novel pyrovalerone cathinone that was among the top five synthetic cathinones seized by weight across Europe in 2022. Since α-PiHP was first reported to the European Union Drugs Agency in December 2016, its use has been linked to severe poisonings and fatalities. The present study employed in vitro and in vivo methods to evaluate the pharmacological effects and pharmacokinetics of α-PiHP in mice, using α-pyrrolidinovalerophenone (α-PVP) as a comparator drug. Our findings show that α-PiHP is a highly potent inhibitor of dopamine (DA) and norepinephrine (NE) reuptake, with a potency equivalent to that of α-PVP for the DA transporter (DAT) and slightly lower for the NE transporter (NET). The strong and targeted inhibition of DAT and NET indicates that α-PiHP has a high potential for misuse. In vivo studies showed that both drugs induced a significant increase in body temperature compared to the control, however, higher doses of α-PiHP (ED₅₀: 4.0 mg/kg) were required to elicit locomotor activity compared to α-PVP (ED₅₀: 1.1 mg/kg). Pharmacokinetic analyses revealed that α-PiHP reached approximately 40 % lower C_max levels in blood and brain, which could explain the lower potency of α-PiHP in inducing locomotor activity. Overall, these findings highlight the need to evaluate the pharmacological characteristics of evolving synthetic cathinones, such as α-PiHP, to better understand the associated health risks.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 412-421"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094402","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":"Infant cognitive home environment as a moderator for the association of prenatal lead on child language","authors":"Amanda C. Wylie ,&nbsp;Michael T. Willoughby ,&nbsp;Rebecca C. Fry ,&nbsp;W. Roger Mills-Koonce ,&nbsp;Sarah J. Short ,&nbsp;Cathi B. Propper","doi":"10.1016/j.neuro.2025.04.010","DOIUrl":"10.1016/j.neuro.2025.04.010","url":null,"abstract":"<div><div>Exposure to lead during early life, including in pregnancy, is toxic to neurodevelopment. Though public health initiatives have resulted in an overall reduction in lead exposure levels, lead remains a significant environmental hazard, requiring innovative efforts to mitigate the burden of early life lead. This study explored whether positive postnatal social experiences in the forms of positive caregiving and a rich cognitive home environment moderate the associations of prenatal lead on child neurodevelopmental outcomes including language skills, effortful control, and executive function skills. We leverage an analytic sample (<em>N</em> = 107) drawn from a prospective cohort of mother-infant dyads. Prenatal lead was measured from maternal urine, positive caregiving from observational methods, and cognitive home environment from a validated questionnaire. Results reveal a negative association of prenatal lead on child language when the cognitive home environment in infancy was poor (<em>β</em>=-0.32, <em>p</em> = 0.04) but not when the cognitive home environment in infancy was rich (<em>β</em>=0.20, <em>p</em> = 0.16). This buffering effect was not observed for the child outcomes of effortful control or executive function skills. Our results encourage future research into the provision of a rich cognitive home environment as a means of mitigating the detrimental effects of prenatal lead exposure on early child language skills.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 306-317"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904539","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":"Mechanisms of developmental neurotoxicity of Dechlorane Plus, a recently identified persistent organic pollutant: An in silico study","authors":"Fuat Karakuş ,&nbsp;Zübeyde Tanrıverdi ,&nbsp;Burak Kuzu","doi":"10.1016/j.neuro.2025.04.013","DOIUrl":"10.1016/j.neuro.2025.04.013","url":null,"abstract":"<div><div>Dechlorane Plus (DP), a polychlorinated flame retardant, has recently been recognized as a persistent organic pollutant. In this study, the molecular mechanisms and targets associated with DP-induced developmental neurotoxicity (DNT) in humans were investigated through network toxicology, multi-level bioinformatics approaches, and molecular docking. Through comprehensive database analysis, 32 potential targets associated with DP-induced DNT were identified. Gene Ontology terms enrichment analysis revealed significant enrichment in pathways related to the nervous system processes, GABA-A receptor complex, and various binding and channel activities. KEGG pathway enrichment analysis indicated that DP-induced DNT is mediated through complex interactions involving neuroactive ligand-receptor interaction pathways. Further analysis using GeneMANIA, STRING, Cytoscape tools, and MCODE identified 11 hub targets, including GABRA1, GABRB1, GABRB3, and GABRG2 as key targets. Molecular docking revealed that DP binds to the GABRB3-GABRA1-GABRG2 protein complex to a degree comparable to the control bicuculline, a potent and selective antagonist of the GABA-A receptor. These findings suggest that DP may have antagonistic effects on the GABA-A receptor, potentially increasing neuronal excitability. This study offers valuable insights into the molecular mechanisms underlying DP-induced DNT and provides data for <em>in vitro</em> or <em>in vivo</em> studies.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 318-327"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907782","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":"A peripheral irritant motor response (PIMR) assay to identify chemical-induced locomotor deficits in larval zebrafish (Danio rerio)","authors":"Demetrius McAtee,&nbsp;Ahmed Abdelmoneim","doi":"10.1016/j.neuro.2025.05.003","DOIUrl":"10.1016/j.neuro.2025.05.003","url":null,"abstract":"<div><div>Zebrafish (<em>Danio rerio</em>) behavioral assays provide valuable insights into the effects of environmental chemicals on the developing nervous system, primarily through motor responses triggered by stimuli-induced CNS activation. However, as these responses rely on the locomotor integrity of larval zebrafish, chemical-induced impairments to their locomotor capacity could obscure behavioral observations and confound findings concerning the developmental neurotoxicity of the tested chemicals. This limitation emphasizes the need for supporting assays designed to specifically evaluate the locomotor capacity of larval zebrafish. In the present study, we evaluated the use of peripheral irritant-elicited motor responses as a method to identify chemical-induced locomotor deficits. The motor activity of 120 hours post-fertilization (hpf) zebrafish larvae exposed to different concentrations of two peripheral stimulants—mustard oil and cinnamon oil—was evaluated. Subsequently, we assessed changes to central (visual and acoustic) and peripheral (irritant) motor responses after tricaine-s (MS-222; neurodepressant) and tubocurarine (neuromuscular blocker) exposures. Additional investigations were also carried out to assess the central and peripheral motor activity of larvae after developmental exposures (114 h) to lead (Pb) and cadmium (Cd)—two suggested developmental neurotoxic environmental contaminants. Our observations revealed that exposure to mustard oil (12.5 µM) elicits the strongest motor response. Larvae exposed to MS-222 showed decreases in motor responses to visual and acoustic stimuli, but the same exposure induced limited effects on motor responses elicited by the peripheral irritant. Exposure to tubocurarine depressed all motor responses examined. Finally, both Pb and Cd exposures induced hypoactivation of central motor responses, but only Cd showed a significant depression in the peripheral irritant motor response (PIMR) in both intact and developmentally deformed larvae. This finding suggests that loss of locomotor capacity might be confounding the behavioral observations associated with Cd exposures. This research underscores the utility of this zebrafish-based PIMR assay in elucidating locomotor impairments induced by chemicals, which may obscure the behavioral findings of motor response assays designed to evaluate developmental neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 344-353"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946650","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":"Urolithin improves α-synuclein aggregation and DNMT1 expression in rotenone model of Parkinson’s disease","authors":"Ankita Devi ,&nbsp;Sharon Munagalasetty ,&nbsp;Pardeep Kumar ,&nbsp;Rahul Kumar ,&nbsp;Vasundhra Bhandari ,&nbsp;Manoj P. Dandekar","doi":"10.1016/j.neuro.2025.04.009","DOIUrl":"10.1016/j.neuro.2025.04.009","url":null,"abstract":"<div><div>α-synuclein aggregation is a key hallmark of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). We examined the multi-targeting effects of urolithin (UA, UB, UC, UD, UE, UM5, and UM6) against α-synuclein aggregation using an <em>in-silico</em> and <em>in-vitro</em> approach. For <em>in-silico</em> analysis, several potential targets were selected like 1XQ8 (α-synuclein monomer), 1H1D (catechol-o-methyltransferase), 2BK3 (monoamine oxidase-B), 3IAM (NADH dehydrogenase), 4I5I (Sirtuin-1), and 5WVO [DNA methyltransferase-1], which play key role in α-synuclein aggregation, levodopa degradation, and mitochondrial dysfunction. In protein-protein docking analysis, 5HF9 (acetylcholinesterase, AChE) was found to interact with 1XQ8 dimer, forming a more stable complex with two additional H-bonds and one salt bridge, which indicates AChE's role as a nucleator in α-synuclein aggregation. In ligand docking and molecular dynamic studies, urolithin-A (UA) formed a more stable complex with 1XQ8, 4I5I, and 5WVO compared to specific inhibitor 1XQ8-ZPD2 and specific activator 4I5I-resveratrol. While other urolithins (UE, UM5, UC, and UD) displayed a more stable complex with 5HF9, 2BK3, 1H1D, and 3IAM compared to specific inhibitor 5HF9-physostigmine, 2BK3-selegiline, 1H1D-BIA, and specific activator 3IAM-resveratrol complexes, respectively. The blood-brain barrier permeability of UA (QPlogBB: −0.97) was predicted to be more than levodopa (QPlogBB: −1.44) and less than rotenone (QPlogBB: 0.08). DNMT1 inhibitor (5-Aza-dC) and rotenone robustly decreased the DNMT1 and α-synuclein expression in Neuro 2 A cells which was significantly reversed by UA treatment at 31.25 µM concentration. These findings indicate the potential of urolithins, specifically UA, UC, UD, UE, and UM5 against α-synuclein aggregation.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 246-262"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882368","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 effects of oral gestational particulate matter 10 exposure: Insights into neurodevelopmental milestones, inhibitory control, adult sociability, and object recognition","authors":"Diego Ruiz-Sobremazas ,&nbsp;Mario Coca ,&nbsp;Miguel Morales-Navas ,&nbsp;Rocío Rodulfo-Cardenas ,&nbsp;Caridad Lopez-Granero ,&nbsp;Maria-Teresa Colomina ,&nbsp;Cristian Perez-Fernandez ,&nbsp;Fernando Sanchez-Santed","doi":"10.1016/j.neuro.2025.04.007","DOIUrl":"10.1016/j.neuro.2025.04.007","url":null,"abstract":"<div><div>Air pollutants have been associated with various neurodevelopmental disorders, with several studies specifically linking Particulate Matter (PM) exposure to attentional and social deficits. This link is even more pronounced when exposure occurs during the prenatal period, as it can disrupt normal brain development. However, while social deficits have been extensively studied during adolescence, their impact on adult social behaviors remains largely unexplored. To investigate these effects, pregnant Wistar rats were exposed throughout gestation (GD1-GD21) to PM₁₀ at a dosage of 200 μg/Kg/day diluted in PBS that was freely drunk. After birth, the pups were evaluated on developmental milestones such as weight progression, ocular opening, and muscular strength. In adulthood, inhibitory control was assessed using the Five Choice Serial Reaction Time Task (5-CSRTT), social behavior using the Three-Chambered Crawley’s Test (3-CT), and object recognition using the Novelty Object Recognition test (NOR). The results indicated that prenatal PM10 exposure is associated with higher birth weight and poorer performance in neuromuscular tests. However, no significant differences were observed in inhibitory control (5-CSRTT) or social behavior (3-CT). Interestingly, prenatally exposed rodents showed heightened novelty responses in the NOR test. In conclusion, gestational exposure to PM₁₀ is related to differences in neurodevelopmental milestones, including weight and muscular strength. While it does not impact adult inhibitory control or social behavior, it influences novelty recognition in later life.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 231-245"},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855225","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":"β-Caryophyllene attenuates cadmium induced neurotoxicity in rats by modulating different cellular signaling pathways","authors":"Ismail Bolat ,&nbsp;Serkan Yildirim ,&nbsp;Yavuz Selim Saglam ,&nbsp;Selim Comakli ,&nbsp;Samet Teki̇n ,&nbsp;Merve Bolat ,&nbsp;Tuba Dogan ,&nbsp;Metin Ki̇li̇cli̇oglu ,&nbsp;Berrah Gozegi̇r","doi":"10.1016/j.neuro.2025.04.006","DOIUrl":"10.1016/j.neuro.2025.04.006","url":null,"abstract":"<div><div>Cadmium (Cd) is a naturally occurring harmful metal that can cause damage to many different tissues and organs in the body. Antioxidant agents are frequently utilized to counteract the harmful impact of this heavy metal on the body. This research explores the neuroprotective role of β-caryophyllene (BCP) in Cd-induced toxicity. Male Wistar rats were categorized into five groups: control, BCP400, Cd, BCP200 +Cd, and BCP400 +Cd. BCP suppressed Cd-induced oxidative damage in brain tissue by regulating the Nrf2/HO-1/SIRT1 signaling pathway. Moreover, BCP alleviates Cd-induced behavioral alterations through SIRT1 activation<del>.</del> Cd increased TNF-α and IL-1β levels and decreased IL-10 levels in brain tissue, whereas BCP suppressed TLR-4/NF-κB/JNK signaling pathway and restored these cytokines to normal levels. In addition, Cd exposure led to increased BAX and Caspase 3 and decreased Bcl-2 levels in neurons, but these proteins approached normal levels thanks to BCP's anti-apoptotic properties. Furthermore, while Beclin-1 and LC3A/B expression levels were increased in neurons of Cd-exposed animals, BCP suppressed these expressions by activating the PI3K/Akt/mTOR signaling pathway. Histopathological, biochemical, and molecular analyses confirmed BCP reduces oxidative stress, inflammation, apoptosis, and autophagy caused by Cd-induced neurotoxicity by regulating various signaling pathways and strengthening the antioxidant defense system. Therefore, we believe that BCP has a high potential as a therapeutic agent against Cd-induced neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 206-217"},"PeriodicalIF":3.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833852","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":"Thymoquinone-loaded solid lipid nanoparticles mitigate 3-Nitropropionic acid-induced mitochondrial dysfunction and oxidative damage via regulating PGC-1α/Nrf2 pathway","authors":"Surekha Ramachandran ,&nbsp;Sumathi Thangarajan","doi":"10.1016/j.neuro.2025.04.005","DOIUrl":"10.1016/j.neuro.2025.04.005","url":null,"abstract":"<div><div>3-Nitropropionic acid (3-NP) is a mitochondrial toxin which causes bilateral striatal lesions in experimental animals, mimicking Huntington’s disease (HD) pathology. The molecular mechanisms underlying 3-NP-induced neuronal death involve mitochondrial dysfunction, transcriptional dysregulation, and impaired antioxidant defense systems. This study investigated the effects of thymoquinone (TQ) encapsulated in solid lipid nanoparticles (NanoTQ), on mitochondrial biogenesis in 3-NP-induced neurotoxicity in the striatum of male Wistar rats. Systemic administration of 3-NP (10 mg/kg) for 14 days inhibited mitochondrial complex enzymes and increased mitochondrial membrane permeability in the striatum. 3-NP exposure significantly altered the translational level of PGC-1α by modifying the expression of p-CREB/TORC1/SIRT1/PPARγ. Additionally, 3-NP exposure significantly reduced striatal levels of BDNF, GDNF, and their downstream effectors. Treatment with NanoTQ (10 and 20 mg/kg) and TQ (80 mg/kg) significantly (<em>P</em> &lt; 0.01) increased mitochondrial complex enzyme activity compared to TQ (40 mg/kg). NanoTQ also significantly (<em>P</em> &lt; 0.01) regulated the expression of regulatory proteins, promoting PGC-1α mediated mitochondrial biogenesis. Furthermore, NanoTQ restored BDNF and GDNF signaling and enhanced the antioxidant defense mechanism by increasing Nrf-2 and HO-1 expression while reducing Keap1 levels in the striatum. In conclusion, NanoTQ effectively mitigated 3-NP-induced neurotoxicity by regulating the mitochondrial biogenesis, neurotrophic factors, and antioxidant defense system, thereby preventing HD-like symptoms in rats.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 191-205"},"PeriodicalIF":3.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829881","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":"Using machine learning to investigate the influence of the prenatal chemical exposome on neurodevelopment of young children","authors":"Gillian England-Mason ,&nbsp;Sarah J. MacEachern ,&nbsp;Kimberly Amador ,&nbsp;Munawar Hussain Soomro ,&nbsp;Anthony J.F. Reardon ,&nbsp;Amy M. MacDonald ,&nbsp;David W. Kinniburgh ,&nbsp;Nicole Letourneau ,&nbsp;Gerald F. Giesbrecht ,&nbsp;Jonathan W. Martin ,&nbsp;Nils D. Forkert ,&nbsp;Deborah Dewey","doi":"10.1016/j.neuro.2025.04.001","DOIUrl":"10.1016/j.neuro.2025.04.001","url":null,"abstract":"<div><div>Research investigating the prenatal chemical exposome and child neurodevelopment has typically focused on a limited number of chemical exposures and controlled for sociodemographic factors and maternal mental health. Emerging machine learning approaches may facilitate more comprehensive examinations of the contributions of chemical exposures, sociodemographic factors, and maternal mental health to child neurodevelopment. A machine learning pipeline that utilized feature selection and ranking was applied to investigate which common prenatal chemical exposures and sociodemographic factors best predict neurodevelopmental outcomes in young children. Data from 406 maternal-child pairs enrolled in the APrON study were used. Maternal concentrations of 32 environmental chemical exposures (<em>i.e.,</em> phthalates, bisphenols, per- and polyfluoroalkyl substances (PFAS), metals, trace elements) measured during pregnancy and 11 sociodemographic factors, as well as measures of maternal mental health and urinary creatinine were entered into the machine learning pipeline. The pipeline, which consisted of a RReliefF variable selection algorithm and support vector machine regression model, was used to identify and rank the best subset of variables predictive of cognitive, language, and motor development outcomes on the Bayley Scales of Infant Development-Third Edition (Bayley-III) at 2 years of age. Bayley-III cognitive scores were best predicted using 29 variables, resulting in a correlation coefficient of r = 0.27 (R²=0.07). For language outcomes, 45 variables led to the best result (r = 0.30; R²=0.09), whereas for motor outcomes 33 variables led to the best result (r = 0.28, R²=0.09). Environmental chemicals, sociodemographic factors, and maternal mental health were found to be highly ranked predictors of cognitive, language, and motor development in young children. Our findings demonstrate the potential of machine learning approaches to identify and determine the relative importance of different predictors of child neurodevelopmental outcomes. Future developmental neurotoxicology research should consider the prenatal chemical exposome as well as sample characteristics such as sociodemographic factors and maternal mental health as important predictors of child neurodevelopment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 218-230"},"PeriodicalIF":3.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844953","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}