Neurotoxicology最新文献

{"title":"Do toenail manganese and iron levels reflect brain metal levels or brain metabolism in welders?","authors":"Gianna Nossa ,&nbsp;Humberto Monsivais ,&nbsp;Chang Geun Lee ,&nbsp;Grace Francis ,&nbsp;Ellen M. Wells ,&nbsp;Jae Hong Park ,&nbsp;Ulrike Dydak","doi":"10.1016/j.neuro.2024.07.007","DOIUrl":"10.1016/j.neuro.2024.07.007","url":null,"abstract":"<div><p>Inhalation of welding fumes can cause metal accumulation in the brain, leading to Parkinsonian-like symptoms. Metal accumulation and altered neurochemical profiles have been observed using magnetic resonance imaging (MRI) in highly exposed welders, being associated with decreased motor function and cognition. While MRI is impractical to use as a health risk assessment tool in occupational settings, toenail metal levels are easier to assess and have been demonstrated to reflect an exposure window of 7–12 months in the past. Yet, it is unclear whether toenail metal levels are associated with brain metal levels or changes in metabolism, which are the root of potential health concerns. This study investigates whether toenail manganese (Mn) and iron (Fe) levels, assessed at several time points, correlate with brain Mn and Fe levels, measured by MRI, as well as brain GABA, glutamate (Glu), and glutathione (GSH) levels, measured by Magnetic Resonance Spectroscopy (MRS), in seventeen Mn-exposed welders. Quantitative T1 and R2* MRI maps of the whole brain, along with GABA, Glu, and GSH MRS measurements from the thalamus and cerebellum were acquired at baseline (T0). Toenail clippings were collected at T0 and every three months after the MRI for a year to account for different exposure periods being reflected by toenail clippings and MRI. Spearman correlations of toenail metal levels were run against brain metal and metabolite levels, but no significant associations were found for Mn at any timepoint. Cerebellar GSH positively correlated with toenail Fe clipped twelve months after the MRI (p = 0.05), suggesting an association with Fe exposure at the time of the MRI. Neither thalamic GABA nor Glu correlated with toenail Fe levels. In conclusion, this study cannot support toenail Mn as a proxy for brain Mn levels or metabolic changes, while toenail Fe appears linked to brain metabolic alterations, underscoring the importance of considering other metals, including Fe, in studying Mn neurotoxicity.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 45-55"},"PeriodicalIF":3.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603976","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":"Male-biased vulnerability of mouse brain tryptophan/kynurenine and glutamate systems to adolescent exposures to concentrated ambient ultrafine particle air pollution","authors":"D.A. Cory-Slechta ,&nbsp;E. Marvin ,&nbsp;K. Welle ,&nbsp;C. Goeke ,&nbsp;D. Chalupa ,&nbsp;G. Oberdörster ,&nbsp;M. Sobolewski","doi":"10.1016/j.neuro.2024.07.004","DOIUrl":"10.1016/j.neuro.2024.07.004","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Air pollution (AP) exposures have been associated with numerous neurodevelopmental and psychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia, all male-biased disorders with onsets from early life to late adolescence/early adulthood. While prior experimental studies have focused on effects of AP exposures during early brain development, brain development actually extends well into early adulthood. The current study in mice sought to extend the understanding of developmental brain vulnerability during adolescence, a later but significant period of brain development and maturation to the ultrafine particulate (UFPs) component of AP, considered its most reactive component. Additionally, it examined adolescent response to UFPs when preceded by earlier developmental exposures, to ascertain the trajectory of effects and potential enhancement or mitigation of adverse consequences. Outcomes focused on shared features associated with multiple neurodevelopmental disorders. For this purpose, C57Bl/6 J mice of both sexes were exposed to ambient concentrated UFPs or filtered air from PND (postnatal day) 4–7 and PND10–13, and again at PND39–42 and 45–49, resulting in 3 exposure postnatal/adolescent treatment groups per sex: Air/Air, Air/UFP, and UFP/UFP. Features common to neurodevelopmental disorders were examined at PND50. Mass exposure concentration from postnatal exposure averaged 44.34 μg/m&lt;sup&gt;3&lt;/sup&gt; and the adolescent exposure averaged 49.18 μg/m&lt;sup&gt;3&lt;/sup&gt;. Male brain showed particular vulnerability to UFP exposures in adolescence, with alterations in frontal cortical and striatal glutamatergic and tryptophan/serotonergic neurotransmitters and concurrent reductions in levels of astrocytes in corpus callosum and in serum cytokine levels, with combined exposures resulting in significant reductions in corpus callosum myelination and serum corticosterone. Reductions in serum corticosterone in males correlated with reductions in neurotransmitter levels, and reductions in striatal glutamatergic function specifically correlated with reductions in corpus callosum astrocytes. UFP-induced changes in neurotransmitter levels in males were mitigated by prior postnatal exposure, suggesting potential adaptation, whereas reductions in corticosterone and in corpus callosum neuropathological effects were further strengthened by combined postnatal and adolescent exposures. UFP-induced changes in females occurred primarily in striatal dopamine systems and as reductions in serum cytokines only in response to combined postnatal and adolescent exposures. Findings in males underscore the importance of more integrated physiological assessments of mechanisms of neurotoxicity. Further, these findings provide biological plausibility for an accumulating epidemiologic literature linking air pollution to neurodevelopmental and psychiatric disorders. As such, they support a need for consideration of the regulati","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 20-35"},"PeriodicalIF":3.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603977","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":"Neurotoxic and behavioral deficit in Drosophila melanogaster exposed to photocatalytic products of Paraquat","authors":"","doi":"10.1016/j.neuro.2024.06.012","DOIUrl":"10.1016/j.neuro.2024.06.012","url":null,"abstract":"<div><p>The Advanced Oxidative Processes have demonstrated potential for application in the degradation of organic pollutants, such as Paraquat (PQ) from water and wastewater, due to their low price, high efficiency, and non-toxic properties. In this study, we investigated whether the photodegradation of PQ with TiO₂ nanotubes reduced its toxicity in <em>Drosophila melanogaster</em>. However, dietary ingestion of degradation products PQ for larvae resulted in a low axial ratio (pupal volume). In the adults, products of photodegradation of PQ exposure markedly diminished climbing ability in a time-dependent manner after 10 days of feeding. In addition, exposure of <em>D. melanogaster</em> to photodegradation of PQ reduced acetylcholinesterase and citrate synthase activities but improved oxidative stress, as evidenced by oxide nitric, protein carbonyl, and lactate production. These results suggest that the photodegradation of PQ with TiO₂ nanotubes produced PQ fragments with higher toxicity than PQ, while the precise mechanism of its action needs further investigation.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 11-19"},"PeriodicalIF":3.4,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563924","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":"Neuroprotective efficacy of the glucocorticoid receptor modulator PT150 in the rotenone mouse model of Parkinson’s disease","authors":"","doi":"10.1016/j.neuro.2024.06.017","DOIUrl":"10.1016/j.neuro.2024.06.017","url":null,"abstract":"<div><p>Parkinson's disease (PD) is the most common neurodegenerative movement disorder worldwide. Current treatments for PD largely center around dopamine replacement therapies and fail to prevent the progression of pathology, underscoring the need for neuroprotective interventions. Approaches that target neuroinflammation, which occurs prior to dopaminergic neuron (DAn) loss in the substantia nigra (SN), represent a promising therapeutic strategy. The glucocorticoid receptor (GR) has been implicated in the neuropathology of PD and modulates numerous neuroinflammatory signaling pathways in the brain. Therefore, we investigated the neuroprotective effects of the novel GR modulator, PT150, in the rotenone mouse model of PD, postulating that inhibition of glial inflammation would protect DAn and reduce accumulation of neurotoxic misfolded ⍺-synuclein protein. C57Bl/6 mice were exposed to 2.5 mg/kg/day rotenone by intraperitoneal injection for 14 days. Upon completion of rotenone dosing, mice were orally treated at day 15 with 30 mg/kg/day or 100 mg/kg/day PT150 in the 14-day post-lesioning incubation period, during which the majority of DAn loss and α-synuclein (α-syn) accumulation occurs. Our results indicate that treatment with PT150 reduced both loss of DAn and microgliosis in the nigrostriatal pathway. Although morphologic features of astrogliosis were not attenuated, PT150 treatment promoted potentially neuroprotective activity in these cells, including increased phagocytosis of hyperphosphorylated α-syn. Ultimately, PT150 treatment reduced the loss of DAn cell bodies in the SN, but not the striatum, and prohibited intra-neuronal accumulation of α-syn. Together, these data indicate that PT150 effectively reduced SN pathology in the rotenone mouse model of PD.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 320-334"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498556","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":"Incomplete autophagy and increased cholesterol synthesis during neuronal cell death caused by a synthetic cannabinoid, CP-55,940","authors":"Hikari Tachibana,&nbsp;Moeka Nomura,&nbsp;Takeshi Funakoshi,&nbsp;Kana Unuma,&nbsp;Toshihiko Aki,&nbsp;Koichi Uemura","doi":"10.1016/j.neuro.2024.06.013","DOIUrl":"10.1016/j.neuro.2024.06.013","url":null,"abstract":"<div><p>There is a propensity for synthetic cannabinoid abuse to spread worldwide. CP-55,940, a synthetic cannabinoid having the ability to activate both CB1 and CB2 receptors, has been shown to induce cell death in neurons as well as other cells. Here we investigate molecular events underling the adverse effects of CP-55,940 on neuronal cells. Exposure of mouse neuroblastoma Neuro2a cells to 10–50 µM CP-55,940 results in concentration-dependent cell death that is not accompanied by an induction of apoptosis. CP-55,940 also stimulates autophagy, but the stimulation is not followed by an increase in autophagic degradation. Transcriptome analysis using DNA microarray revealed the increased expression of genes for the cholesterol biosynthesis pathway that is associated with the activation of SREBP-2, the master transcriptional regulator of cholesterol biosynthesis. However, free cholesterol is localized mainly to cytoplasmic structures, although it is localized to the plasma membrane in healthy cells. Thus, cellular trafficking of cholesterol seems to be somewhat disrupted in CP-55,940 stimulated cells. These results show for the first time that CP-55,940 stimulates autophagy as well as cholesterol biosynthesis, although not all the processes involved in the cellular response to CP-55,940 seem to be complete in these cells.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 215-221"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469695","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":"Vitamin D attenuates monosodium glutamate-induced behavioural anomalies, metabolic dysregulation, cholinergic impairment, oxidative stress, and astrogliosis in rats","authors":"Ismail Gbadamosi ,&nbsp;Emmanuel Olusola Yawson ,&nbsp;Justice Akesinro ,&nbsp;Opeyemi Adeleke ,&nbsp;Olorunfemi Tokunbo ,&nbsp;Olawande Bamisi ,&nbsp;Rukayat Ibrahim-Abdulkareem ,&nbsp;Paul Awoniran ,&nbsp;Rukayat Gbadamosi ,&nbsp;Ezra Lambe ,&nbsp;Aminat Atoyebi ,&nbsp;Adedamola Aminat Bayo-Olugbami ,&nbsp;Taiwo Adekemi Abayomi ,&nbsp;Tolulope Timothy Arogundade","doi":"10.1016/j.neuro.2024.06.015","DOIUrl":"10.1016/j.neuro.2024.06.015","url":null,"abstract":"<div><h3>Background</h3><p>Monosodium glutamate (MSG) is a commonly used flavor enhancer that has raised concerns due to its potential adverse effects on various organs. This study explored the neuroprotective potential of Vitamin D, a beneficial micronutrient, in mitigating MSG-induced neurotoxicity.</p></div><div><h3>Materials and methods</h3><p>Adult male Wistar rats were categorized into five groups: control (2 ml/kg PBS orally for 30 days), MSG (40 mg/kg orally for 30 days), VIT-D (oral cholecalciferol; 500 IU/kg for 30 days), MSG+VIT-D (MSG for 30 days followed by VIT-D for another 30 days), and VIT-D/MSG (concurrent VIT-D and MSG for 30 days). The rats underwent neurobehavioral, histochemical, and biochemical analyses following the treatments.</p></div><div><h3>Results</h3><p>MSG treatment caused a decline in both long and short-term memory, along with reduced exploratory and anxiogenic behavior, mitigated by vitamin D treatment. MSG exposure also induced impaired behavior, dyslipidemia, oxidative stress, lipid peroxidation, altered cholinergic transmission, and increased chromatolysis and neuroinflammation in the frontal cortex, hippocampus, and cerebellum.</p></div><div><h3>Conclusions</h3><p>VIT-D demonstrated a mitigating effect on MSG-induced adverse outcomes, highlighting its potential to attenuate neurodegenerative cascades. This investigation contributes to understanding MSG-associated neurotoxicity and suggests vitamin D as a valuable and potential intervention for neuroprotection.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 297-309"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534923","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":"Gray matter morphometric biomarkers for distinguishing manganese-exposed welders from healthy adults revealed by source-based morphometry","authors":"Jiayu Wu ,&nbsp;Qiaoying Zhang ,&nbsp;Mingyue Ma ,&nbsp;Yan Dong ,&nbsp;Pengfeng Sun ,&nbsp;Ming Gao ,&nbsp;Peng Liu ,&nbsp;Xiaoping Wu","doi":"10.1016/j.neuro.2024.07.002","DOIUrl":"10.1016/j.neuro.2024.07.002","url":null,"abstract":"<div><h3>Background</h3><p>Chronic overexposure to manganese (Mn) may result in neurotoxicity, which is characterized by motor and cognitive dysfunctions. This study aimed to utilize multivariate source-based morphometry (SBM) to explore the biomarkers for distinguishing Mn-exposed welders from healthy controls (HCs).</p></div><div><h3>Methods</h3><p>High-quality 3D T1-weighted MRI scans were obtained from 45 Mn-exposed full-time welders and 33 age-matched HCs in this study. After extracting gray matter structural covariation networks by SBM, multiple classic interaction linear models were applied to investigate distinct patterns in welders compared to HCs, and Z-transformed loading coefficients were compared between the two groups. A receiver operating characteristic (ROC) curve was used to identify potential biomarkers for distinguishing Mn-exposed welders from HCs. Additionally, we assessed the relationships between clinical features and gray matter volumes in the welders group.</p></div><div><h3>Results</h3><p>A total of 78 subjects (45 welders, mean age 46.23±4.93 years; 33 HCs, mean age 45.55±3.40 years) were evaluated. SBM identified five components that differed between the groups. These components displayed lower loading weights in the basal ganglia, thalamus, default mode network (including the lingual gyrus and precuneus), and temporal lobe network (including the temporal pole and parahippocampus), as well as higher loading weights in the sensorimotor network (including the supplementary motor cortex). ROC analysis identified the highest classification power in the thalamic network.</p></div><div><h3>Conclusions</h3><p>Altered brain structures might be implicated in Mn overexposure-related disturbances in motivative modulation, cognitive control and information integration. These results encourage further studies that focus on the interaction mechanisms, including the basal ganglia network, thalamic network and default mode network. Our study identified potential neurobiological markers in Mn-exposed welders and illustrated the utility of a multivariate method of gray matter analysis.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 222-229"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538213","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":"Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology","authors":"Fatema Currim ,&nbsp;Reeya Tanwar ,&nbsp;Josephine M. Brown-Leung ,&nbsp;Neha Paranjape ,&nbsp;Jennifer Liu ,&nbsp;Laurie H. Sanders ,&nbsp;Jonathan A. Doorn ,&nbsp;Jason R. Cannon","doi":"10.1016/j.neuro.2024.06.016","DOIUrl":"10.1016/j.neuro.2024.06.016","url":null,"abstract":"<div><p>Parkinson’s disease (PD) is a debilitating neurodegenerative disease affecting millions of individuals worldwide. Hallmark features of PD pathology are the formation of Lewy bodies in neuromelanin-containing dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc), and the subsequent irreversible death of these neurons. Although genetic risk factors have been identified, around 90 % of PD cases are sporadic and likely caused by environmental exposures and gene-environment interaction. Mechanistic studies have identified a variety of chemical PD risk factors. PD neuropathology occurs throughout the brain and peripheral nervous system, but it is the loss of DAergic neurons in the SNpc that produce many of the cardinal motor symptoms. Toxicology studies have found specifically the DAergic neuron population of the SNpc exhibit heightened sensitivity to highly variable chemical insults (both in terms of chemical structure and mechanism of neurotoxic action). Thus, it has become clear that the inherent neurobiology of nigral DAergic neurons likely underlies much of this neurotoxic response to broad insults. This review focuses on inherent neurobiology of nigral DAergic neurons and how such neurobiology impacts the primary mechanism of neurotoxicity. While interactions with a variety of other cell types are important in disease pathogenesis, understanding how inherent DAergic biology contributes to selective sensitivity and primary mechanisms of neurotoxicity is critical to advancing the field. Specifically, key biological features of DAergic neurons that increase neurotoxicant susceptibility.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 266-287"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534922","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":"Prenatal endocrine-disrupting chemicals exposure and impact on offspring neurodevelopment: A systematic review and meta-analysis","authors":"Ziyi Yang ,&nbsp;Jie Zhang ,&nbsp;Mingbo Wang ,&nbsp;Xin Wang ,&nbsp;Huahua Liu ,&nbsp;Feng Zhang ,&nbsp;Hong Fan","doi":"10.1016/j.neuro.2024.07.006","DOIUrl":"10.1016/j.neuro.2024.07.006","url":null,"abstract":"<div><h3>Purpose</h3><p>Considering that endocrine disruptors have certain effects on fetal growth, we conducted a systematic review of epidemiological literature to elucidate the correlation between exposure to endocrine-disrupting chemicals during pregnancy and the neurodevelopment of offspring.</p></div><div><h3>Method</h3><p>We systematically explored PubMed, Web of Science, and CINAHL databases from inception to April 4, 2023. References from pertinent studies were reviewed, and data regarding the link between maternal prenatal EDC exposure and offspring neurological development were compiled. A domain-based approach was used to evaluate studies of neurodevelopmental effects in children ≤3 years old by two reviewers, including cognition, motor, behavior, language, and non-verbal ability.</p></div><div><h3>Results</h3><p>A comprehensive search yielded 45,373 articles, from which 48 articles, involving 26,005 mother-child pairs, met the criteria and were subsequently included in our analysis. The results revealed that EDC exposure during pregnancy had a significant impact on offspring neurobehavior development, especially in cognition, motor, and language. Our findings indicated adverse associations between prenatal exposure to metals and offspring cognition (before 12 months: β coefficient: −0.28; 95 % CI, −0.50 to −0.06; 1–3 years old: β coefficient: −0.55; 95 % CI: −1.08 to −0.02). Furthermore, metals (β coefficient: −0.71; 95 % CI: −1.23 to −0.19) and phthalates (β coefficient: −0.69; 95 % CI: −1.05 to −0.33) exposure exhibited detrimental effects on motor development from1–3 years old, while poly-fluoroalkyl substances were linked to the disruption of offspring language development (β coefficient: −1.01; 95 % CI: −1.90 to −0.11) within this timeframe. Additionally, exposure to EDCs during pregnancy had a negative impact on cognition development among girls from 12 to 36 months of age (β coefficient: −0.53; 95 % CI: −1.01 to −0.06).</p></div><div><h3>Conclusion</h3><p>Prenatal exposure to EDCs, especially metals, phthalates and, poly-fluoroalkyl substances, was associated with disrupting the development of offspring neurobehavior in the short and long term. Additionally, cognitive development showed gender differences due to prenatal endocrine-disrupting chemicals exposure.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 335-357"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627208","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":"Childhood exposure to organophosphate pesticides: Functional connectivity and working memory in adolescents","authors":"Yuanyuan Gao ,&nbsp;Rihui Li ,&nbsp;Qianheng Ma ,&nbsp;Joseph M. Baker ,&nbsp;Stephen Rauch ,&nbsp;Robert B. Gunier ,&nbsp;Ana M. Mora ,&nbsp;Katherine Kogut ,&nbsp;Asa Bradman ,&nbsp;Brenda Eskenazi ,&nbsp;Allan L. Reiss ,&nbsp;Sharon K. Sagiv","doi":"10.1016/j.neuro.2024.06.011","DOIUrl":"10.1016/j.neuro.2024.06.011","url":null,"abstract":"<div><h3>Background</h3><p>Early life exposure to organophosphate (OP) pesticides is linked with adverse neurodevelopment and brain function in children. However, we have limited knowledge of how these exposures affect functional connectivity, a measure of interaction between brain regions. To address this gap, we examined the association between early life OP pesticide exposure and functional connectivity in adolescents.</p></div><div><h3>Methods</h3><p>We administered functional near-infrared spectroscopy (fNIRS) to 291 young adults with measured prenatal or childhood dialkylphosphates (DAPs) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal study of women recruited during pregnancy and their offspring. We measured DAPs in urinary samples collected from mothers during pregnancy (13 and 26 weeks) and children in early life (ages 6 months, 1, 2, 3, and 5 years). Youth underwent fNIRS while they performed executive function and semantic language tasks during their 18-year-old visit. We used covariate-adjusted regression models to estimate the associations of prenatal and childhood DAPs with functional connectivity between the frontal, temporal, and parietal regions, and a mediation model to examine the role of functional connectivity in the relationship between DAPs and task performance.</p></div><div><h3>Results</h3><p>We observed null associations of prenatal and childhood DAP concentrations and functional connectivity for the entire sample. However, when we looked for sex differences, we observed an association between childhood DAPs and functional connectivity for the right interior frontal and premotor cortex after correcting for the false discovery rate, among males, but not females. In addition, functional connectivity appeared to mediate an inverse association between DAPs and working memory accuracy among males.</p></div><div><h3>Conclusion</h3><p>In CHAMACOS, a secondary analysis showed that adolescent males with elevated childhood OP pesticide exposure may have altered brain regional connectivity. This altered neurofunctional pattern in males may partially mediate working memory impairment associated with childhood DAP exposure.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 206-214"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440761","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}