Neurotoxicology and teratology最新文献

{"title":"Oxidative stress as a potential mechanism linking gestational phthalates exposure to cognitive development in infancy.","authors":"Kaegan Ortlund, Susan L Schantz, Andréa Aguiar, Francheska M Merced-Nieves, Megan L Woodbury, Dana E Goin, Antonia M Calafat, Ginger L Milne, Stephanie M Eick","doi":"10.1016/j.ntt.2024.107397","DOIUrl":"https://doi.org/10.1016/j.ntt.2024.107397","url":null,"abstract":"<p><strong>Background: </strong>Gestational exposure to phthalates, endocrine disrupting chemicals widely used in consumer products, has been associated with poor recognition memory in infancy. Oxidative stress may represent one pathway linking this association. Hence, we examined whether exposure to phthalates was associated with elevated oxidative stress during pregnancy, and whether oxidative stress mediates the relationship between phthalate exposure and recognition memory.</p><p><strong>Methods: </strong>Our analysis included a subset of mother-child pairs enrolled in the Illinois Kids Development Study (IKIDS, N = 225, recruitment years 2013-2018). Concentrations of 12 phthalate metabolites were quantified in 2nd trimester urine samples. Four oxidative stress biomarkers (8-isoprostane-PGF_2α, 2,3-dinor-5,6-dihydro-8-isoPGF_2α, 2,3-dinor-8-isoPGF_2α, and prostaglandin-F_2α) were measured in 2nd and 3rd trimester urine. Recognition memory was evaluated at 7.5 months, with looking times to familiar and novel stimuli recorded via infrared eye-tracking. Novelty preference (proportion of time looking at a novel stimulus when paired with a familiar one) was considered a measure of recognition memory. Linear mixed effect models were used to estimate associations between monoethyl phthalate (MEP), sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of di(isononyl) phthalate metabolites (ΣDINP), and sum of anti-androgenic phthalate metabolites (ΣAA) and oxidative stress biomarkers. Mediation analysis was performed to assess whether oxidative stress biomarkers mediated the effect of gestational phthalate exposure on novelty preference.</p><p><strong>Results: </strong>The average maternal age at delivery was 31 years and approximately 50 % of participants had a graduate degree. A natural log unit increase in ΣAA, ΣDINP, and ΣDEHP was associated with a statistically significant increase in 8-isoPGF_2α, 2,3-dinor-5,6-dihydro-8-isoPGF_2α, and 2,3-dinor-8-isoPGF_2α. The association was greatest in magnitude for ΣAA and 2,3-dinor-5,6-dihydro-8-isoPGF_2α (β = 0.45, 95 % confidence interval = 0.14, 0.76). The relationship between ΣAA, ΣDINP, ΣDEHP, and novelty preference was partially mediated by 2,3-dinor-8-isoPGF_2α.</p><p><strong>Conclusions: </strong>Gestational exposure to some phthalates is positively associated with oxidative stress biomarkers, highlighting one mechanistic pathway through which these chemicals may impair early cognitive development.</p>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372381","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":"Assessment of adverse childhood experiences in adolescents from a rural agricultural community: Associations with depressive symptoms and psychosocial problems","authors":"","doi":"10.1016/j.ntt.2024.107396","DOIUrl":"10.1016/j.ntt.2024.107396","url":null,"abstract":"<div><div>The main goal of this study was to determine the prevalence of adverse childhood experiences (ACEs) among Latino adolescents from an agricultural community and to examine how it may impact their neuropsychiatric functioning. This research particularly assessed the association between ACEs and depression, as well as ACEs and psychosocial problems. The study sample consisted of 852 adolescents treated at a rural primary care clinic with a comprehensive ACE screening protocol that assesses for ACEs, depressed mood, and psychosocial functioning during every annual Well-Child Visit. Study results showed that ACEs were relatively common among participants with 64 % endorsing having experienced at least one ACE. Approximately 23 % of participants screened positive for depressed mood and 11 % for psychosocial problems. ACEs were found to have significant associations with both depression symptoms and with psychosocial problems. Males were found to have less depression symptoms than females among subjects with exposure to most ACE types, and older age was associated with lower psychosocial impairment. Study participants live in an agricultural community and are likely exposed to both chemical and non-chemical stressors. The exposure to ACEs and chemical environmental stressors may interact with pathological synergy to alter their biobehavioral development. Further research is needed to understand the “rules” for which stressors at what dose and at what stage of development place youth at greatest risk.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350800","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":"Cellular responses to developmental exposure to pyriproxyfen in chicken model: Contrasting embryos with and without exencephaly","authors":"","doi":"10.1016/j.ntt.2024.107395","DOIUrl":"10.1016/j.ntt.2024.107395","url":null,"abstract":"<div><div>The insecticide pyriproxyfen (PPF), commonly used in drinking water, has already been described as a potential neurotoxic agent in non-target organisms, particularly during embryonic development. Consequently, exposure to PPF can lead to congenital anomalies in the central nervous system. Therefore, understanding the impact of this insecticide on developing neural cells is a relevant concern that requires attention. Thus, this study aimed to investigate the effects of PPF on the proliferation, differentiation, migration, and cell death of neural cells by comparing embryos that develop exencephaly with normal embryos, after exposure to this insecticide. Chicken embryos, used as a study model, were exposed to concentrations of 0.01 and 10 mg/L PPF on embryonic day E1 and analyzed on embryonic day E10. Exposed embryos received 50 μL of PPF diluted in vehicle solution, and control embryos received exclusively 50 μL of vehicle solution. After exposure, embryos were categorized into control embryos, embryos with exencephaly exposed to PPF, and embryos without exencephaly exposed to PPF. The results showed that although the impact was differentiated in the forebrain and midbrain, both brain vesicles were affected by PPF exposure, and this was observed in embryos with and without exencephaly. The most evident changes observed in embryos with exencephaly were DNA damage accompanied by alterations in cell proliferation, increased apoptosis, and reduced neural differentiation and migration. Embryos without exencephaly showed DNA damage and reduced cell proliferation and migration. These cellular events directly interfered with the density and thickness of neural cell layers. Together, these results suggest that PPF exposure causes cellular damage during neurogenesis, regardless of whether embryos display or do not display external normal morphology. This nuanced understanding provides important insights into the neurotoxicity of PPF and its potential effects on inherent events in neurogenesis.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292168","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":"Neuroinflammation and oxidative redox imbalance drive memory dysfunction in adolescent rats prenatally exposed to Datura Stramonium","authors":"","doi":"10.1016/j.ntt.2024.107394","DOIUrl":"10.1016/j.ntt.2024.107394","url":null,"abstract":"<div><div>Although there have been reports indicating that <em>Datura Stramonium</em> (<em>D. stramonium</em>) may induce anticholinergic and neuropsychiatry effects, the compound is still being used for recreational and medicinal purposes while ingestion during pregnancy has been documented. Intriguingly, minimal studies have investigated the potential neurotoxic impact of <em>D. stramonium</em> exposure at various stages of gestation, including its potential implication on neurophysiological well-being later in life. The present study, therefore, examined spontaneous working memory and the expression of specific neurochemicals modulating crucial neural processes in adolescent rats exposed to high and low <em>D. stramonium</em> doses during different stages of gestation. Pregnant rats were orally infused with 150- or 500- mg/kg/day of <em>D. stramonium</em> either during mid- (second week; days 8–14) or late- (third week; days 15–21) gestation, while control rats received PBS at dosing periods. Behavioral characterization of offspring between postnatal days (PD) 40 and 41 in the Y-maze revealed that <em>D. stramonium</em> perturbed spatial working memory in rats, although locomotor activity was generally unaltered. In addition to SOD and nitric oxide downregulation, induction of oxidative stress in the hippocampus and prefrontal cortex (PFC) of young adult rats prenatally exposed to <em>D. stramonium</em> was corroborated by depletion of key antioxidant regulatory elements glutathione peroxidase, glutathione reductase and catalase, which was accompanied by lipid peroxidation shown by increased MDA levels. Whereas increased expression of acetylcholinesterase and LDH was seen in adolescent rats prenatally infused <em>D. stramonium</em>, acetylcholine levels were downregulated in both hippocampal and PFC lysates, suggesting cholinergic and metabolic dysfunctions. Immunohistochemical labelling of GFAP and IBA-1 revealed increased expression of reactive astrocytes and microglia respectively, while the accompanying TNFα upregulation in both the hippocampus (dentate gyrus) and PFC causally linked intrauterine <em>D. stramonium</em> exposure with neuroinflammatory responses postnatally. Overall, our data correlated postnatal spatial working memory dysfunction evoked by <em>D. stramonium</em> exposure during critical stages of embryonic development to oxidative redox impairment, cholinergic disruption and neuroinflammatory perturbations in rats.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292169","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":"Through a teratological lens: A narrative review of exposure to stress and drugs of abuse during pregnancy on neurodevelopment","authors":"","doi":"10.1016/j.ntt.2024.107384","DOIUrl":"10.1016/j.ntt.2024.107384","url":null,"abstract":"<div><p>Teratological research shows that both prenatal stress and prenatal substance exposure have a significant impact on neurodevelopmental outcomes in children. Using human research, the purpose of this narrative review is to explore the degree to which these exposures may represent complex prenatal and postnatal risks for the development of cognition and behavior in children. An understanding of the HPA axis and its function during pregnancy as well as the types and operationalization of prenatal stress provide a context for understanding the direct and indirect mechanisms by which prenatal stress affects brain and behavior development. In turn, prenatal substance exposure studies are evaluated for their importance in understanding variables that indicate a potential interaction with prenatal stress including reactivity to novelty, arousal, and stress reactivity during early childhood. The similarities and differences between prenatal stress exposure and prenatal substance exposure on neurodevelopmental outcomes including arousal and emotion regulation, cognition, behavior, stress reactivity, and risk for psychopathology are summarized. Further considerations for teratological studies of prenatal stress and/or substance exposure include identifying and addressing methodological challenges, embracing the complexity of pre-and postnatal environments in the research, and the importance of incorporating parenting and resilience into future studies.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073428","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":"Differences in withdrawal symptoms, microglia activity, and cognitive functioning in rats exposed to continuous low-dose heroin in-utero","authors":"","doi":"10.1016/j.ntt.2024.107385","DOIUrl":"10.1016/j.ntt.2024.107385","url":null,"abstract":"<div><h3>Introduction</h3><p>Opioid use during pregnancy and subsequent neonatal opioid withdrawal syndrome (NOWS) have been associated with poor developmental outcomes including cognitive functioning. Less is known about the underlying molecular effects of prenatal opioid exposure and subsequent withdrawal; however, given the recent increase in NOWS cases, there is a pressing need to better understand these effects, which may partially explain cognitive deficits that have been observed in both preclinical NOWS models and patients with NOWS. This study evaluated the effects of prenatal heroin exposure and subsequent precipitated withdrawal symptoms on microglial reactivity in the nucleus accumbens (NAc), dorsal hippocampus (HC), and ventral tegmental area (VTA) in rat neonates, as well as cognitive functioning at three developmental time points using the Morris Water Maze (MWM) task.</p></div><div><h3>Methods</h3><p>Heroin or saline (2 mg/kg) was randomly assigned and administered to six pregnant Sprague Dawley rat dams <em>via</em> osmotic minipump. A total of 63 rat neonates underwent naloxone-precipitated (5 mg/kg, subcutaneous injection) withdrawal testing at postnatal day 10 (PN10). Following withdrawal testing, neonates were randomly assigned to undergo perfusion and subsequent immunohistochemistry experiments to fluoresce Iba-1 for microglia detection, or to undergo the MWM task at three separate developmental time points (PN21–23; PN37; PN60) for cognitive testing.</p></div><div><h3>Results</h3><p>Results suggest that <em>in-utero</em> heroin exposure led to an increase in ultrasonic vocalizations during naloxone-precipitated withdrawal; a sensitive index of withdrawal in rat neonates. Additional results suggest increased microglial reactivity in the HC and VTA, but not the NAc, as well as reduced performance during the MWM in the group exposed to heroin <em>in-utero</em>.</p></div><div><h3>Discussion</h3><p>Together, these data suggest that <em>in-utero</em> opioid exposure is associated with microglial reactivity in brain regions associated with learning and memory, and may be associated with later cognitive deficits. Further research is needed to characterize these findings, which may inform future therapeutic strategies for this vulnerable population.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056132","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":"Adolescent exposure to bisphenol-a antagonizes androgen regulation of social behavior in male mice","authors":"","doi":"10.1016/j.ntt.2024.107374","DOIUrl":"10.1016/j.ntt.2024.107374","url":null,"abstract":"<div><p>Social behavior is sexually dimorphic, which is regulated by gonadal hormones in the brain. Our recent study found that exposure to low doses of bisphenol-A (BPA) during adolescence, permanently alters social behavior in adult male mice, but the underlying mechanisms remain unclear. Using adolescent gonadectomy (GDX) male mice with testosterone propionate (TP, 0.5 mg/kg) supplement (TP-GDX), this study showed that BPA antagonized promoting effects of TP on social interaction, sexual behavior, and aggression in GDX mice. BPA eliminated the reversal effects of TP on GDX-induced decrease in the number of immunoreactive to arginine vasopressin (AVP-ir) neurons in the medial amygdala (MeA) and the levels of AVP receptor 1a (V1aR) in the MeA and the nucleus accumbens (NAc). In addition, BPA removed down-regulation in the levels of dopamine (DA) transporter (DAT) and DA receptor 1 (DR1) in the NAc of TP-GDX mice. BPA exposure reduced testosterone (T) levels in the brain and serum and the expression of androgen receptor (AR) protein in the amygdala and striatum of sham-operated and TP-GDX males. These results suggest that adolescent exposure to BPA inhibits regulation of androgen in AVP and DA systems of the brain regions associated with social behavior, and thus alters social behaviors of adult male mice.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889799","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 buprenorphine-naloxone exposure and fetal neurobehavior","authors":"Lauren M. Jansson ,&nbsp;Krystle McConnell ,&nbsp;Martha L. Velez ,&nbsp;Nancy Spencer ,&nbsp;Lorraine Milio ,&nbsp;Jeannie Leoutsakos ,&nbsp;Janet A. DiPietro","doi":"10.1016/j.ntt.2024.107368","DOIUrl":"10.1016/j.ntt.2024.107368","url":null,"abstract":"<div><h3>Background</h3><p>Buprenorphine-naloxone treatment may confer substantial benefits for the treatment of opioid use disorder (OUD) during pregnancy including lower risk for overdose/death, less diversion potential and reduced use of other substances. Treatment may also result in less severe Neonatal Abstinence Syndrome (NAS), but little is known about the effects of this medication on fetal neurodevelopment.</p></div><div><h3>Methods</h3><p>The purpose of the current study is to evaluate neurobehaviors among fetuses exposed to buprenorphine-naloxone at four time points over the second and third trimesters of gestation in pregnant women with OUD on buprenorphine-naloxone therapy. Sixty minutes of continuous fetal monitoring via fetal actocardiograph with a single wide array abdominal transducer took place at times of peak and trough buprenorphine-naloxone levels in 24 pregnant women. Data collection, which included measures of fetal heart rate and motor activity, was conducted between 24 and 36 weeks gestation, with the majority (84.6%) monitored at two or more gestational ages. Medication dose and other substance use was monitored throughout the study and infant NAS severity was assessed.</p></div><div><h3>Results</h3><p>Fetal heart rate (FHR), FHR variability, accelerations in FHR, and motor activity were suppressed when buprenorphine-naloxone levels were at pharmacologic peak as compared to trough concentrations at 36 weeks, but not earlier in gestation. Maternal medication dose was unrelated to infant NAS severity.</p></div><div><h3>Conclusions</h3><p>Conclusions: There were evident subclinical fetal neurophysiological responses at times of peak maternal buprenorphine/naloxone levels in later gestation, similar to those previously described for buprenorphine only. Further studies evaluating the effects of these changes in fetal neurobehaviors on the longer-term infant development are needed.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437226","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":"Neurotoxicity assessment of the herbicide pethoxamid in zebrafish (Danio rerio) embryos/larvae","authors":"Cole D. English ,&nbsp;Emma Ivantsova ,&nbsp;Lev Avidan ,&nbsp;Kira Kazi ,&nbsp;Eliana Maira Agostini Valle ,&nbsp;Isaac Konig ,&nbsp;Christopher J. Martyniuk","doi":"10.1016/j.ntt.2024.107369","DOIUrl":"10.1016/j.ntt.2024.107369","url":null,"abstract":"<div><p>Pethoxamid, a member of the chloroacetamide herbicide family, is a recently approved chemical for pre- or post-emergence weed control; however, toxicity data for sublethal effects in aquatic organisms exposed to pethoxamid are non-existent in literature. To address this, we treated zebrafish embryos/larvae to pethoxamid over a 7-day period post-fertilization and evaluated several toxicological endpoints associated with oxidative stress and neurotoxicity. Continuous pethoxamid exposure did not affect survival nor hatch success in embryos/larvae for 7 days up to 1000 μg L⁻¹. Exposure to pethoxamid did not affect embryonic ATP-linked respiration, but it did reduce non-mitochondrial respiration at the highest concentration tested. We also noted a significant increase in both apoptosis and levels of reactive oxygen species (ROS) in larvae zebrafish following exposure to pethoxamid. Increases in apoptosis and ROS, however, were not correlated with any altered gene expression pattern for apoptotic and oxidative damage response transcripts. To assess neurotoxicity potential, we measured behavior and several transcripts implicated in neural processes in the central nervous system. While locomotor activity of larval zebrafish was affected by pethoxamid exposure (hyperactivity was observed at concentrations below 1 μg L⁻¹, and hypoactivity was noted at higher exposures to 10 and 100 μg L⁻¹ pethoxamid), there were no effects on steady state mRNA abundance for neurotoxicity-related transcripts tested. This data contributes to knowledge regarding exposure risks for chloroacetamide-based herbicides and is the first study investigating sublethal toxicity for this newly registered herbicide.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534916","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":"Tyrosinase inhibition prevents non-coplanar polychlorinated biphenyls and polybrominated diphenyl ethers-induced hyperactivity in developing zebrafish: Interaction between pigmentation and neurobehavior","authors":"","doi":"10.1016/j.ntt.2024.107373","DOIUrl":"10.1016/j.ntt.2024.107373","url":null,"abstract":"<div><p>Non-coplanar polychlorinated biphenyl (PCB) mixture Aroclor 1254 and polybrominated diphenyl ether (PBDE) BDE-47 are known to impede neurogenesis and neuronal development. We previously reported that exposure to PCB and PBDE leads to increased embryonic movement in zebrafish by decreasing dopamine levels. In this study, we studied the connection between the melanin and dopamine synthesis pathways in this context. Both genetic and chemical inhibition of tyrosinase, the rate-limiting enzyme in melanin synthesis, not only led to reduced pigmentation but also inhibit PCB/PBDE-induced embryonic hyperactivity. Furthermore, PCB and PBDE rarely affected tyrosinase expression in the potential pigment cells, suggesting that these compounds reduce dopamine through enzymatic regulation, including a competitive interaction for the substrate tyrosine. Our results provide new insights into the interactions between melanogenesis and dopaminergic neuronal activity, which may contribute to understanding the mechanisms underlying PCB/PBDE toxicity in developing organisms.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724097","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}