Neurotoxicology and teratology最新文献

{"title":"Prenatal buprenorphine/naloxone exposure and neonatal neurobehavioral functioning: A preliminary report","authors":"Martha L. Velez ,&nbsp;Krystle McConnell ,&nbsp;Nancy Spencer ,&nbsp;Lina M. Montoya ,&nbsp;Lauren M. Jansson","doi":"10.1016/j.ntt.2024.107400","DOIUrl":"10.1016/j.ntt.2024.107400","url":null,"abstract":"<div><h3>Introduction</h3><div>Although prescription of buprenorphine/naloxone during pregnancy is gaining acceptance, buprenorphine monotherapy is more often used due to the scarce knowledge of the effects of the combined medications on the fetus and neonate. Evaluation of neurobehavioral functioning of neonates prenatally exposed to buprenorphine/naloxone is lacking. The NICU Network Neurobehavioral Scale (NNNS) has been used to evaluate neurobehavioral functioning, stress responses, and regulatory capacities of neonates at risk for altered development due to prenatal stressors. This pilot study presents a descriptive analysis of the neurobehavioral functioning among neonates exposed in utero to buprenorphine/naloxone, as well as maternal characteristics and factors present during their pregnancy.</div></div><div><h3>Methods</h3><div>Participants were pregnant parents receiving comprehensive treatment for opioid use disorder (OUD) and obstetric care, choosing buprenorphine/naloxone treatment with singleton, uncomplicated pregnancies. Participants provided confidential urine specimens for legal and illegal psychoactive substances according to protocol. Maternal psychiatric disorders and psychiatric medications as well as weekly dosing records were obtained for the duration of study participation. The NNNS was administered to 16 full-term neonates on days 3,14 and 30 of life.</div></div><div><h3>Results</h3><div>Mean summary scores for 12 neurobehavioral domains (attention, arousal, self-regulation, handling, quality of movement, excitability, lethargy, non-optimal reflexes, asymmetrical reflexes, hypertonia, hypotonia and stress/abstinence syndrome) are presented for neonates prenatally exposed to buprenorphine/naloxone at three time points during the first month of life. Several maternal factors that can influence the functioning of the neonate were presented in this sample including smoking cigarettes (94 %), a psychiatric diagnosis (87.5 %), positive urinalysis for legal or illegal substances during treatment (56.2 %).</div></div><div><h3>Conclusions</h3><div>This report provides preliminary information regarding the neurobehavioral functioning of neonates exposed to buprenorphine/naloxone over the first month of life, including consideration of maternal factors. However, future research with a larger sample and controlling for different neonate and maternal factors is necessary to confirm these preliminary findings.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"106 ","pages":"Article 107400"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567631","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":"Trans-Ferulic acid reduces the sedative activity of diazepam in thiopental sodium-induced sleeping mice: A potential GABAergic transmission","authors":"Md. Shimul Bhuia ,&nbsp;Md. Sakib Al Hasan ,&nbsp;Raihan Chowdhury ,&nbsp;Siddique Akber Ansari ,&nbsp;Irfan Aamer Ansari ,&nbsp;Muhammad Torequl Islam","doi":"10.1016/j.ntt.2024.107403","DOIUrl":"10.1016/j.ntt.2024.107403","url":null,"abstract":"<div><div><em>trans</em>-Ferulic acid (TFA), a bioactive compound found in many plants, has been recognized for its diverse pharmacological activities, including potential neurological benefits. Previous studies suggest that TFA exerts anxiolytic effects <em>via</em> GABAergic pathways. This study aimed to investigate the sedative effects of TFA and its possible molecular mechanisms through <em>in vivo</em> and <em>in silico</em> approaches. Adult <em>Swiss</em> mice were randomly divided into six groups (<em>n</em> = 7): control (vehicle), standard (DZP: Diazepam at 3 mg/kg, p.o.), three test groups (TFA at 25, 50, and 75 mg/kg, p.o.), and a combination group (TFA: 50 mg/kg with DZP: 3 mg/kg, p.o.). Thirty minutes post-treatment, thiopental sodium (TS) at 40 mg/kg was administered to induce sedation, and latency as well as duration of sleep, were observed for up to 4 h. <em>In silico</em> studies were conducted with GABA_A receptor subunits (α1 and β2) to elucidate the possible molecular interactions. The results demonstrated that TFA significantly reduced latency and extended sleep duration in a dose-dependent manner compared to the control. Additionally, TFA combined with DZP further significantly (<em>p</em> &lt; 0.001) enhanced these effects. <em>In silico</em> analysis revealed that TFA and DZP exhibited strong binding affinities with the GABA_A receptor subunits (α1 and β2) in the identical binding sites, with binding energies of −6.8 and − 8.7 kcal/mol, respectively. Collectively, TFA exerted a mild sedative effect in TS-induced sleeping mice and modulated the activity of DZP, likely through interactions with GABA_A receptors. TFA showed promising activity as a potential candidate for managing sleep disorders such as insomnia.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"106 ","pages":"Article 107403"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639166","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":"Bisphenol F-induced precocious genesis of aggressive neurobehavioral response is associated with heightened monoamine oxidase activity and neurodegeneration in zebrafish brain","authors":"Suvam Bhoi ,&nbsp;Prerana Sarangi ,&nbsp;Lilesh Kumar Pradhan ,&nbsp;Pradyumna Kumar Sahoo ,&nbsp;Bhabani Sankar Sahoo ,&nbsp;Sai Aparna ,&nbsp;Sangeeta Raut ,&nbsp;Saroj Kumar Das","doi":"10.1016/j.ntt.2024.107402","DOIUrl":"10.1016/j.ntt.2024.107402","url":null,"abstract":"<div><div>The production and use of plastics and plastics products has increased dramatically in recent decades. Moreover, their unprotected disposal into ambient life sustaining environment poses a significant health risk. Bisphenol F (BPF) an alternative to bisphenol A (BPA) has been extensively employed for making of plastics. Recent reports have documented the neurotoxic potential of BPF through induction of altered neurochemical profile, microglia-astrocyte-mediated neuroinflammation, oxidative stress, transformed neurobehavioral response, cognitive dysfunction, etc. In the present study, our approach was to understand the underlying mechanism of BPF-persuaded genesis of aggressive neurobehavioral response in zebrafish. The basic findings advocated a temporal transformation in native explorative behaviour and progressive induction of aggressive behavioural response in zebrafish following exposure to BPF. Our neurobehavioral findings supported the argument of oxidative stress-mediated neuromorphological transformation in the periventricular grey zone (PGZ) of the zebrafish brain. In line with earlier reports, our findings also showed that heightened monoamine oxidase (MAO) activity and downregulation in tyrosine hydroxylase expression in the zebrafish brain is associated with the precocious genesis of aggressive neurobehavioral response in zebrafish brain. Our findings also shed light on BPF-instigated apoptotic neuronal death as revealed by augmented chromatin condensation and cleaved caspase-3 expression. Further observation showed that the downregulation of NeuN (a marker of post-mitotic mature neuron) expression provided substantial neurotoxicity, leading to neurodegeneration in the PGZ region of the zebrafish brain. These basic findings grossly advocate that BPF acts as a potent neurotoxicant in transmuting native neurobehavioral response through the induction of oxidative stress, heightened MAO activity and neuromorphological transformation in the zebrafish brain.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"106 ","pages":"Article 107402"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504798","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":"Lasting effects of adolescent social instability stress on dendritic morphology in the nucleus accumbens in female and male Long Evans rats","authors":"Ashutosh Patel ,&nbsp;Abdulhai Aljaabary ,&nbsp;YiJie Yuan ,&nbsp;Pardis Asgari ,&nbsp;Craig D.C. Bailey ,&nbsp;Cheryl M. McCormick","doi":"10.1016/j.ntt.2024.107401","DOIUrl":"10.1016/j.ntt.2024.107401","url":null,"abstract":"<div><div>Social instability stress (SS) in adolescence in rats leads to long-lasting changes in social behaviour and reward-related behaviour relative to control rats. Given the role of the nucleus accumbens (NAc) in such behaviours, we investigated the morphology of medium spiny neurons (MSNs), which are most neurons in the NAc, in adult female and male rats exposed to SS in adolescence. Irrespective of sex, SS rats had increased number of dendritic spines in both the core and shell regions of the NAc (2.3 % and 18.1 % increase, respectively). In the core, SS rats had a 16 % reduction in the total dendritic lengths of MSNs, whereas in the shell, SS rats had a greater dendritic length closer to the soma, and particularly in SS female rats, whereas the opposite was found farther from the soma (SS 10.6 % &gt; CTL overall). Although the extent to which such structural changes may underlie the enduring effects of SS in adolescence requires investigation, the results add to evidence that changes to the social environment in adolescence can determine adult neuronal structural.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"106 ","pages":"Article 107401"},"PeriodicalIF":2.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal tobacco and tobacco-Cannabis co-exposure and unpredictability in maternal anger/hostility: Implications for toddler reactivity","authors":"Madison R. Kelm ,&nbsp;Pamela Schuetze ,&nbsp;Rina D. Eiden","doi":"10.1016/j.ntt.2024.107399","DOIUrl":"10.1016/j.ntt.2024.107399","url":null,"abstract":"<div><div>Tobacco and cannabis are frequently used together during pregnancy. However, relatively little is known about how co-use and related maternal risk factors impact toddler reactivity. One understudied risk factor is maternal experience of anger/hostility, despite evidence suggesting that individuals who use substances experience more anger/hostility. In addition, mood unpredictability in anger/hostility (MUA), a relatively novel construct, may be particularly important for mothers who use substances as they attempt to cut down or quit during pregnancy and may also impact toddler reactivity. Importantly, prenatal exposures may also impact toddler outcomes via continued postnatal exposure and infant reactivity. We examined a conceptual model linking prenatal tobacco and tobacco-cannabis co-use, maternal anger/hostility, and unpredictability in anger/hostility with toddler reactivity in a sample (<em>N</em> = 247 at recruitment, 190 at toddler age; <em>N</em> = 247 for model testing) of dyads recruited during the first trimester of pregnancy into a tobacco group (use of combustible cigarettes; including sub-group of women who also used cannabis) and a non-substance use group. Results indicated a direct effect of prenatal co-exposure on blunted toddler reactivity for males only. Mothers who used substances prenatally had the highest levels of anger/hostility and MUA. Prenatal anger/hostility and MUA were associated with higher reactivity at infancy which in turn, was associated with higher toddler reactivity. Prenatal co-exposure and higher prenatal maternal anger/hostility was associated with continued postnatal exposure to cannabis which in turn, was associated with higher reactivity at toddlerhood. Results highlight the importance of examining prenatal co-exposure and continued postnatal cannabis exposure as well as associated maternal risk factors such as anger/hostility and MUA for toddler developmental outcomes.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"106 ","pages":"Article 107399"},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470821","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":"Editorial: Passing the torch: The next chapter for Neurotoxicology and Teratology.","authors":"Gale A Richardson","doi":"10.1016/j.ntt.2024.107398","DOIUrl":"https://doi.org/10.1016/j.ntt.2024.107398","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":" ","pages":"107398"},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470820","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":"Oxidative stress as a potential mechanism linking gestational phthalates exposure to cognitive development in infancy","authors":"Kaegan E Ortlund ,&nbsp;Susan L. Schantz ,&nbsp;Andréa Aguiar ,&nbsp;Francheska M. Merced-Nieves ,&nbsp;Megan L. Woodbury ,&nbsp;Dana E. Goin ,&nbsp;Antonia M. Calafat ,&nbsp;Ginger L. Milne ,&nbsp;Stephanie M. Eick","doi":"10.1016/j.ntt.2024.107397","DOIUrl":"10.1016/j.ntt.2024.107397","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>Our analysis included a subset of mother-child pairs enrolled in the Illinois Kids Development Study (IKIDS, <em>N</em> = 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"106 ","pages":"Article 107397"},"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":"Javier I. Rosado,&nbsp;Jean Kesnold Mesidor,&nbsp;Sheena Chege,&nbsp;Yuxia Wang,&nbsp;Lisandra Torres,&nbsp;Gregg D. Stanwood","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":"106 ","pages":"Article 107396"},"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":"Maico Roberto Luckmann,&nbsp;Evelise Maria Nazari","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":"106 ","pages":"Article 107395"},"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":"Olawande Bamisi ,&nbsp;Adesua Olukayode Oluwalabani ,&nbsp;Tolulope Timothy Arogundade ,&nbsp;Olayemi Joseph Olajide","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":"106 ","pages":"Article 107394"},"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}