The brain is especially vulnerable to environmental influences during the perinatal period. While the effects of environmental factors are usually studied in isolation, it is more typical to be exposed to multiple influences during early development, necessitating study of synergistic actions on the developing brain. Both maternal infection and endocrine disrupting phthalates can decrease cell number in the medial prefrontal cortex (mPFC), a region critical for executive functioning. In the present study, groups of pregnant Long Evans rats were treated with either (1) 100 μg/kg (i.p.) lipopolysaccharide (LPS) on embryonic days 15 and 16 combined with a low-dose (1 mg/kg) phthalate mixture throughout gestation and the neonatal period, (2) LPS alone, (3) phthalates alone, or (4) neither phthalates nor LPS (control). Neurons and glial cells were stereologically quantified in the mPFC. The adult offspring previously exposed to LPS or phthalates alone had reduced mPFC neuron number in exposed males, but not females, while the combination treatment did not produce significant effects. In males, LPS alone also reduced the number of glia in the mPFC. Additionally, the combination of LPS and phthalates resulted in fewer pregnancies to term and decreased litter size. These results provide insight into how common environmental factors can interact to alter the developmental trajectory of the mPFC.
{"title":"Effects of maternal LPS and developmental exposure to an environmentally relevant phthalate mixture on neuron number in the rat medial prefrontal cortex","authors":"V.R. Riesgo , E.P. Sellinger , A.S. Brinks , J.M. Juraska , J. Willing","doi":"10.1016/j.ntt.2024.107370","DOIUrl":"10.1016/j.ntt.2024.107370","url":null,"abstract":"<div><p>The brain is especially vulnerable to environmental influences during the perinatal period. While the effects of environmental factors are usually studied in isolation, it is more typical to be exposed to multiple influences during early development, necessitating study of synergistic actions on the developing brain. Both maternal infection and endocrine disrupting phthalates can decrease cell number in the medial prefrontal cortex (mPFC), a region critical for executive functioning. In the present study, groups of pregnant Long Evans rats were treated with either (1) 100 μg/kg (i.p.) lipopolysaccharide (LPS) on embryonic days 15 and 16 combined with a low-dose (1 mg/kg) phthalate mixture throughout gestation and the neonatal period, (2) LPS alone, (3) phthalates alone, or (4) neither phthalates nor LPS (control). Neurons and glial cells were stereologically quantified in the mPFC. The adult offspring previously exposed to LPS or phthalates alone had reduced mPFC neuron number in exposed males, but not females, while the combination treatment did not produce significant effects. In males, LPS alone also reduced the number of glia in the mPFC. Additionally, the combination of LPS and phthalates resulted in fewer pregnancies to term and decreased litter size. These results provide insight into how common environmental factors can interact to alter the developmental trajectory of the mPFC.</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":"https://www.sciencedirect.com/science/article/pii/S0892036224000527/pdfft?md5=179e5bec0ca1a4698b92ce7de968b047&pid=1-s2.0-S0892036224000527-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534915","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}
Pub Date : 2024-07-01DOI: 10.1016/j.ntt.2024.107372
{"title":"Introduction to “Effects of per- and polyfluoroalkyl substances (PFAS) within a developmental context”","authors":"","doi":"10.1016/j.ntt.2024.107372","DOIUrl":"10.1016/j.ntt.2024.107372","url":null,"abstract":"","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":"141698354","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}
Pub Date : 2024-07-01DOI: 10.1016/j.ntt.2024.107371
We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9–12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (n = 133; n = 34 non-substance exposed, n = 37 exposed to tobacco only, n = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (p = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely.
{"title":"Prenatal tobacco and tobacco-cannabis co-exposure: Relationship with attention and memory in middle childhood","authors":"","doi":"10.1016/j.ntt.2024.107371","DOIUrl":"10.1016/j.ntt.2024.107371","url":null,"abstract":"<div><p>We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9–12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (<em>n</em> = 133; <em>n</em> = 34 non-substance exposed, <em>n</em> = 37 exposed to tobacco only, <em>n</em> = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (<em>p</em> = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely.</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":"https://www.sciencedirect.com/science/article/pii/S0892036224000539/pdfft?md5=243dc560bfc67cccefab339cd3997818&pid=1-s2.0-S0892036224000539-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545100","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}
Alcohol use, which alters the epigenome, increases the probability that it could affect subsequent generations, even if they were never directly exposed to ethanol or even in utero.
We explored the effects of parental ethanol exposure before conception on behavioral changes in the offspring. Considering the role of Monoamine oxidase-B (MAO-B) in dopamine turnover in the prefrontal cortex (PFC) and its influence on behavior, and taking into account that ethanol exposure could alter MAO-B, we assessed the protein levels in the offspring.
Male and female rats were exposed to ethanol for 30 days and then allowed ten days of abstinence. Afterward, they were mated with either control or ethanol-exposed rats. The F1 and F2 male offspring underwent tests to assess behavioral changes. Additionally, the levels of MAO-B in the PFC were evaluated.
Results revealed that in the F1, anxiety increased only in the bi-parental ethanol-exposed male offspring in the elevated plus maze test (p < 0.05), while depressive-like behavior rose only in maternal and bi-parental ethanol-exposed offspring (p < 0.01). However, compulsive-like behavior increased in all ethanol-exposed offspring (p < 0.01). No significant phenotypic changes were observed in the F2. The levels of MAO-B in the PFC increased in the maternal (p < 0.05) and bi-parental ethanol-exposed offspring (p < 0.01).
Our study demonstrates that parental ethanol exposure, even in the days preceding mating, adversely affects behaviors and induces molecular changes in the brain. Given these findings, it becomes imperative to monitor children exposed to parental (especially maternal) ethanol for the prevention of mental disorders.
饮酒会改变表观基因组,从而增加影响后代的可能性,即使他们从未直接接触过乙醇,甚至在子宫内也没有接触过乙醇。我们探讨了父母在受孕前接触乙醇对后代行为变化的影响。考虑到单胺氧化酶-B(MAO-B)在前额叶皮质(PFC)多巴胺转换中的作用及其对行为的影响,并考虑到乙醇暴露可能会改变 MAO-B,我们评估了后代体内的蛋白质水平。雌雄大鼠暴露于乙醇中 30 天,然后戒酒 10 天。之后,它们与对照组或乙醇暴露组大鼠交配。F1和F2雄性后代接受测试以评估行为变化。此外,还对PFC中的MAO-B水平进行了评估。结果显示,在 F1 中,只有双亲暴露于乙醇的雄性后代在高架加迷宫测试中焦虑增加(p
{"title":"Preconception ethanol exposure changes anxiety, depressive and checking-like behavior and alter the expression levels of MAO-B in male offspring","authors":"Mohammad Basir Asefi , Amirhossein Heidari , Arman Hajikarim-Hamedani , Zahra Mousavi , Ghorbangol Ashabi , Mitra-Sadat Sadat-Shirazi , Mohammad-Reza Zarrindast","doi":"10.1016/j.ntt.2024.107367","DOIUrl":"10.1016/j.ntt.2024.107367","url":null,"abstract":"<div><p>Alcohol use, which alters the epigenome, increases the probability that it could affect subsequent generations, even if they were never directly exposed to ethanol or even in utero.</p><p>We explored the effects of parental ethanol exposure before conception on behavioral changes in the offspring. Considering the role of Monoamine oxidase-B (MAO-B) in dopamine turnover in the prefrontal cortex (PFC) and its influence on behavior, and taking into account that ethanol exposure could alter MAO-B, we assessed the protein levels in the offspring.</p><p>Male and female rats were exposed to ethanol for 30 days and then allowed ten days of abstinence. Afterward, they were mated with either control or ethanol-exposed rats. The F1 and F2 male offspring underwent tests to assess behavioral changes. Additionally, the levels of MAO-B in the PFC were evaluated.</p><p>Results revealed that in the F1, anxiety increased only in the bi-parental ethanol-exposed male offspring in the elevated plus maze test (<em>p</em> < 0.05), while depressive-like behavior rose only in maternal and bi-parental ethanol-exposed offspring (<em>p</em> < 0.01). However, compulsive-like behavior increased in all ethanol-exposed offspring (<em>p</em> < 0.01). No significant phenotypic changes were observed in the F2. The levels of MAO-B in the PFC increased in the maternal (<em>p</em> < 0.05) and bi-parental ethanol-exposed offspring (p < 0.01).</p><p>Our study demonstrates that parental ethanol exposure, even in the days preceding mating, adversely affects behaviors and induces molecular changes in the brain. Given these findings, it becomes imperative to monitor children exposed to parental (especially maternal) ethanol for the prevention of mental disorders.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311277","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}
Pub Date : 2024-05-01DOI: 10.1016/j.ntt.2024.107358
{"title":"The 48th Annual Meeting of the Developmental Neurotoxicology Society (DNTS)","authors":"","doi":"10.1016/j.ntt.2024.107358","DOIUrl":"https://doi.org/10.1016/j.ntt.2024.107358","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141240699","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}
Pub Date : 2024-05-01DOI: 10.1016/j.ntt.2024.107356
Charles V. Vorhees , Robyn M. Amos-Kroohs , Michael T. Williams
Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES conditions often experience more stress than those in other SES groups. There are multiple model systems of early environmental stress (EES), one of which is reduced cage bedding. Here we tested the effects of both prenatal and lactational EES in rats on a range of long-term behavioral and cognitive outcomes. There were persistent reductions in body weight in the EES rats in both sexes. The behavioral results showed no effects on learning and memory using tests of spatial learning or cognitive flexibility in the Morris water maze, egocentric learning in the Cincinnati water maze, or working memory in the radial-arm maze. There were no effects on basic open-field activity, elevated zero-maze, or forced swim test, but EES rats had reduced time in the dark side of the light/dark test. When rats were drug challenged in the open-field with d-amphetamine or MK-801, there were no differential responses to d-amphetamine, but the EES group under responded compared with the drug-induced hyperactivity in the control group in both males and females. The objective was to establish a developmental stress model that induced cognitive deficits and to the extent that this method did not cause such effects it was not the model we sought. However, the data showed several long-term effects of EES, including the reduced response to the irreversible NMDA antagonist MK-801. This effect merits further investigation.
发育压力,包括较低的社会经济地位(SES),会引起下丘脑-垂体-肾上腺轴的失调,并导致压力反应性的长期变化。社会经济地位较低的儿童往往比其他社会经济地位群体的儿童承受更多的压力。早期环境应激(EES)有多种模型系统,其中之一就是减少笼中垫被。在这里,我们测试了产前和哺乳期环境应激对大鼠一系列长期行为和认知结果的影响。EES大鼠的体重在雌雄大鼠中均持续下降。行为结果显示,莫里斯水迷宫中的空间学习测试或认知灵活性测试、辛辛那提水迷宫中的自我中心学习测试或径向臂迷宫中的工作记忆测试均未对大鼠的学习和记忆产生影响。对大鼠的基本开场活动、高架零迷宫或强迫游泳测试没有影响,但 EES 大鼠在光/暗测试中的暗侧时间减少。用d-安非他明或MK-801对大鼠进行开场药物挑战时,大鼠对d-安非他明的反应没有差异,但与药物诱导的对照组相比,EES组的雌雄大鼠反应不足。我们的目标是建立一个能诱发认知障碍的发育压力模型,如果这种方法没有造成这种影响,那么它就不是我们所寻求的模型。然而,数据显示了EES的几种长期效应,包括对不可逆NMDA拮抗剂MK-801的反应减弱。这种效应值得进一步研究。
{"title":"Long-term effects of Preweaning environmental impoverishment on neurobehavioral and neurocognitive outcomes in Sprague Dawley rats: An early environmental stress model","authors":"Charles V. Vorhees , Robyn M. Amos-Kroohs , Michael T. Williams","doi":"10.1016/j.ntt.2024.107356","DOIUrl":"10.1016/j.ntt.2024.107356","url":null,"abstract":"<div><p>Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES conditions often experience more stress than those in other SES groups. There are multiple model systems of early environmental stress (EES), one of which is reduced cage bedding. Here we tested the effects of both prenatal and lactational EES in rats on a range of long-term behavioral and cognitive outcomes. There were persistent reductions in body weight in the EES rats in both sexes. The behavioral results showed no effects on learning and memory using tests of spatial learning or cognitive flexibility in the Morris water maze, egocentric learning in the Cincinnati water maze, or working memory in the radial-arm maze. There were no effects on basic open-field activity, elevated zero-maze, or forced swim test, but EES rats had reduced time in the dark side of the light/dark test. When rats were drug challenged in the open-field with d-amphetamine or MK-801, there were no differential responses to d-amphetamine, but the EES group under responded compared with the drug-induced hyperactivity in the control group in both males and females. The objective was to establish a developmental stress model that induced cognitive deficits and to the extent that this method did not cause such effects it was not the model we sought. However, the data showed several long-term effects of EES, including the reduced response to the irreversible NMDA antagonist MK-801. This effect merits further investigation.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892240","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}
Pub Date : 2024-05-01DOI: 10.1016/j.ntt.2024.107355
Francheska M. Merced-Nieves , Bonnie Lerman , Elena Colicino , Michelle Bosquet Enlow , Robert O. Wright , Rosalind J. Wright
Background
Psychosocial stress and psychopathology frequently co-occur, with patterns differing by race and ethnicity. We used statistical mixtures methodology to examine associations between prenatal stress and child temperament in N = 382 racially and ethnically diverse maternal-child dyads to disentangle associations among maternal stressful life events, maternal psychological functioning in pregnancy, childhood neurobehavior, and maternal race and ethnicity.
Methods
This study utilized data from a longitudinal pregnancy cohort, PRogramming of Intergenerational Stress Mechanisms (PRISM). Mothers completed the Lifetime Stressor Checklist-Revised, Edinburgh Postnatal Depression Scale, and Spielberger State-Trait Anxiety Scale during pregnancy. When their children were 3–5 years of age, they completed the Children's Behavior Questionnaire, which yields three temperament dimensions: Negative Affectivity (NA), Effortful Control (EC), and Surgency (S). We used weighted quantile sum regression to derive a weighted maternal stress index encompassing lifetime stress and depression and anxiety symptoms and examined associations between the resulting stress index and child temperament. Differential contributions of individual stress domains by race and ethnicity also were examined.
Results
Mothers self-identified as Black/Black Hispanic (46.1 %), non-Black Hispanic (31.9 %), or non-Hispanic White (22 %). A higher maternal stress index was significantly associated with increased child NA (β = 0.72 95 % CI = 0.35, 1.10). Lifetime stress was the strongest contributor among Hispanic (36.7 %) and White (17.8 %) mothers, whereas depressive symptoms in pregnancy was the strongest contributor among Black (16.7 %) mothers.
Conclusion
Prenatal stress was most strongly associated with negative affectivity in early childhood. Consideration of multiple stress measures as a mixture accounted for differential contributions of individual stress domains by maternal race and ethnicity. These findings may help elucidate the etiology of racial/ethnic disparities in childhood neurobehavior.
背景:社会心理压力和精神病理学经常同时存在,不同种族和民族的模式也不尽相同。我们使用统计混合物方法研究了 N = 382 个不同种族和民族的母婴二元组合中产前压力与儿童气质之间的关联,以厘清母亲生活压力事件、母亲孕期心理功能、儿童神经行为以及母亲种族和民族之间的关联:本研究利用了妊娠期纵向队列 "代际压力机制研究"(PRISM)的数据。母亲在怀孕期间填写了终生压力检查表-修订版、爱丁堡产后抑郁量表和斯皮尔伯格状态-特征焦虑量表。在孩子 3-5 岁时,他们填写了儿童行为问卷,其中包括三个气质维度:该问卷可得出三个气质维度:消极情绪(NA)、努力控制(EC)和暴躁(S)。我们使用加权量子和回归法得出了包含终生压力、抑郁和焦虑症状的加权母亲压力指数,并研究了由此得出的压力指数与儿童气质之间的关联。此外,还研究了不同种族和族裔对各个压力领域的贡献差异:母亲自我认同为黑人/西班牙裔黑人(46.1%)、非西班牙裔黑人(31.9%)或非西班牙裔白人(22%)。产妇压力指数越高,儿童 NA 的增加越明显(β = 0.72 95 % CI = 0.35, 1.10)。在西班牙裔(36.7%)和白人(17.8%)母亲中,终生压力是最大的影响因素,而在黑人(16.7%)母亲中,孕期抑郁症状是最大的影响因素:结论:产前压力与幼儿期的消极情绪关系最为密切。将多种压力测量方法作为一种混合物进行考虑,可以解释母亲的种族和族裔对单个压力领域的不同贡献。这些发现可能有助于阐明儿童神经行为中种族/民族差异的病因。
{"title":"Maternal lifetime stress and psychological functioning in pregnancy is associated with preschoolers' temperament: Exploring effect modification by race and ethnicity","authors":"Francheska M. Merced-Nieves , Bonnie Lerman , Elena Colicino , Michelle Bosquet Enlow , Robert O. Wright , Rosalind J. Wright","doi":"10.1016/j.ntt.2024.107355","DOIUrl":"10.1016/j.ntt.2024.107355","url":null,"abstract":"<div><h3>Background</h3><p>Psychosocial stress and psychopathology frequently co-occur, with patterns differing by race and ethnicity. We used statistical mixtures methodology to examine associations between prenatal stress and child temperament in <em>N</em> = 382 racially and ethnically diverse maternal-child dyads to disentangle associations among maternal stressful life events, maternal psychological functioning in pregnancy, childhood neurobehavior, and maternal race and ethnicity.</p></div><div><h3>Methods</h3><p>This study utilized data from a longitudinal pregnancy cohort, PRogramming of Intergenerational Stress Mechanisms (PRISM). Mothers completed the Lifetime Stressor Checklist-Revised, Edinburgh Postnatal Depression Scale, and Spielberger State-Trait Anxiety Scale during pregnancy. When their children were 3–5 years of age, they completed the Children's Behavior Questionnaire, which yields three temperament dimensions: Negative Affectivity (NA), Effortful Control (EC), and Surgency (S). We used weighted quantile sum regression to derive a weighted maternal stress index encompassing lifetime stress and depression and anxiety symptoms and examined associations between the resulting stress index and child temperament. Differential contributions of individual stress domains by race and ethnicity also were examined.</p></div><div><h3>Results</h3><p>Mothers self-identified as Black/Black Hispanic (46.1 %), non-Black Hispanic (31.9 %), or non-Hispanic White (22 %). A higher maternal stress index was significantly associated with increased child NA (β = 0.72 95 % CI = 0.35, 1.10). Lifetime stress was the strongest contributor among Hispanic (36.7 %) and White (17.8 %) mothers, whereas depressive symptoms in pregnancy was the strongest contributor among Black (16.7 %) mothers.</p></div><div><h3>Conclusion</h3><p>Prenatal stress was most strongly associated with negative affectivity in early childhood. Consideration of multiple stress measures as a mixture accounted for differential contributions of individual stress domains by maternal race and ethnicity. These findings may help elucidate the etiology of racial/ethnic disparities in childhood neurobehavior.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892241","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}
Pub Date : 2024-04-20DOI: 10.1016/j.ntt.2024.107353
Taylor S. Campbell, Katelyn Donoghue, Tania L. Roth
Aversive caregiving in early life is a risk factor for aberrant brain and behavioral development. This outcome is related to epigenetic dysregulation of the brain-derived neurotrophic factor (Bdnf) gene. The Bdnf gene encodes for BDNF, a neurotrophin involved in early brain development, neural plasticity, learning, and memory. Recent work suggests that exercise may be neuroprotective in part by supporting BDNF protein and gene expression, making it an exciting target for therapeutic interventions. To our knowledge, exercise has never been studied as a therapeutic intervention in preclinical rodent models of caregiver maltreatment. To that end, the current study investigated the effect of an adult voluntary wheel running intervention on Bdnf methylation and expression in the prefrontal cortex of rats who experienced aversive caregiving in infancy. We employed a rodent model (Long Evans rats) wherein rat pups experienced intermittent caregiver-induced stress from postnatal days 1–7 and were given voluntary access to a running wheel (except in the control condition) from postnatal days 70–90 as a young adulthood treatment intervention. Our results indicate that maltreatment and exercise affect Bdnf gene methylation in an exon, CG site, and sex-specific manner. Here we add to a growing body of evidence of the ability for our experiences, including exercise, to permeate the brain. Keywords: Early life stress, Bdnf, exercise, prefrontal cortex.
{"title":"Unlocking the epigenome: Stress and exercise induced Bdnf regulation in the prefrontal cortex","authors":"Taylor S. Campbell, Katelyn Donoghue, Tania L. Roth","doi":"10.1016/j.ntt.2024.107353","DOIUrl":"https://doi.org/10.1016/j.ntt.2024.107353","url":null,"abstract":"<div><p>Aversive caregiving in early life is a risk factor for aberrant brain and behavioral development. This outcome is related to epigenetic dysregulation of the brain-derived neurotrophic factor (<em>Bdnf</em>) gene. The <em>Bdnf</em> gene encodes for BDNF, a neurotrophin involved in early brain development, neural plasticity, learning, and memory. Recent work suggests that exercise may be neuroprotective in part by supporting BDNF protein and gene expression, making it an exciting target for therapeutic interventions. To our knowledge, exercise has never been studied as a therapeutic intervention in preclinical rodent models of caregiver maltreatment. To that end, the current study investigated the effect of an adult voluntary wheel running intervention on <em>Bdnf</em> methylation and expression in the prefrontal cortex of rats who experienced aversive caregiving in infancy. We employed a rodent model (Long Evans rats) wherein rat pups experienced intermittent caregiver-induced stress from postnatal days 1–7 and were given voluntary access to a running wheel (except in the control condition) from postnatal days 70–90 as a young adulthood treatment intervention. Our results indicate that maltreatment and exercise affect <em>Bdnf</em> gene methylation in an exon, CG site, and sex-specific manner. Here we add to a growing body of evidence of the ability for our experiences, including exercise, to permeate the brain. Keywords: Early life stress, Bdnf, exercise, prefrontal cortex.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0892036224000357/pdfft?md5=9a91a4cc0d5697c51502f242d71dca60&pid=1-s2.0-S0892036224000357-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140647271","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}
Pub Date : 2024-04-16DOI: 10.1016/j.ntt.2024.107352
Stine Søgaard Normann , Iben Have Beck , Flemming Nielsen , Marianne Skovsager Andersen , Niels Bilenberg , Tina Kold Jensen , Helle Raun Andersen
Background
Organophosphates and pyrethroids are two major groups of insecticides used for crop protection worldwide. They are neurotoxicants and exposure during vulnerable windows of brain development may have long-term impact on human neurodevelopment. Only few longitudinal studies have investigated associations between prenatal exposure to these substances and intelligence quotient (IQ) at school age in populations with low, mainly dietary, exposure.
Objective
To investigate associations between maternal urinary concentrations of insecticide metabolites at gestational week 28 and IQ in offspring at 7-years of age.
Materials and methods
Data was derived from the Odense Child Cohort (OCC). Metabolites of chlorpyrifos (TCPy) and pyrethroids (3-PBA, cis- and trans-DCCA, 4-F-3PBA, cis-DBCA) were measured in maternal urine collected at gestational week (GW) 28. An abbreviated version of the Danish Wechsler Intelligence Scale for Children fifth edition (WISC-V) consisting of four subtests to estimate full scale IQ (FSIQ) was administered by trained psychologists. Data were analyzed by use of multiple linear regression and adjusted for confounders.
Results
812 mother/child-pairs were included. Median concentrations were 0.21 μg/L for 3-PBA, 1.67 μg/L for TCPy and the mean IQ for children were 99.4. Null association between maternal 3-PBA and child IQ at 7 years was seen, but with trends suggesting an inverse association. There was a significant association for maternal TCPy and child IQ at mid-level exposure. Trans-DCCA above the level of detection (LOD) was also associated with slightly lower child IQ, but the association was also not statistically significant.
Conclusions
We found no significant associations between maternal 3-PBA metabolites and child IQ at 7 years, but with trends suggesting an inverse association. A non-significant trend between maternal TCPy exposure and child IQ in 7-year-children was seen even in this low exposed population. Given the widespread exposure and increasing use of insecticides, this should be elaborated in future studies.
{"title":"Prenatal exposure to pyrethroids and chlorpyrifos and IQ in 7-year-old children from the Odense Child Cohort","authors":"Stine Søgaard Normann , Iben Have Beck , Flemming Nielsen , Marianne Skovsager Andersen , Niels Bilenberg , Tina Kold Jensen , Helle Raun Andersen","doi":"10.1016/j.ntt.2024.107352","DOIUrl":"https://doi.org/10.1016/j.ntt.2024.107352","url":null,"abstract":"<div><h3>Background</h3><p>Organophosphates and pyrethroids are two major groups of insecticides used for crop protection worldwide. They are neurotoxicants and exposure during vulnerable windows of brain development may have long-term impact on human neurodevelopment. Only few longitudinal studies have investigated associations between prenatal exposure to these substances and intelligence quotient (IQ) at school age in populations with low, mainly dietary, exposure.</p></div><div><h3>Objective</h3><p>To investigate associations between maternal urinary concentrations of insecticide metabolites at gestational week 28 and IQ in offspring at 7-years of age.</p></div><div><h3>Materials and methods</h3><p>Data was derived from the Odense Child Cohort (OCC). Metabolites of chlorpyrifos (TCPy) and pyrethroids (3-PBA, cis- and trans-DCCA, 4-F-3PBA, cis-DBCA) were measured in maternal urine collected at gestational week (GW) 28. An abbreviated version of the Danish Wechsler Intelligence Scale for Children fifth edition (WISC-V) consisting of four subtests to estimate full scale IQ (FSIQ) was administered by trained psychologists. Data were analyzed by use of multiple linear regression and adjusted for confounders.</p></div><div><h3>Results</h3><p>812 mother/child-pairs were included. Median concentrations were 0.21 μg/L for 3-PBA, 1.67 μg/L for TCPy and the mean IQ for children were 99.4. Null association between maternal 3-PBA and child IQ at 7 years was seen, but with trends suggesting an inverse association. There was a significant association for maternal TCPy and child IQ at mid-level exposure. <em>Trans</em>-DCCA above the level of detection (LOD) was also associated with slightly lower child IQ, but the association was also not statistically significant.</p></div><div><h3>Conclusions</h3><p>We found no significant associations between maternal 3-PBA metabolites and child IQ at 7 years, but with trends suggesting an inverse association. A non-significant trend between maternal TCPy exposure and child IQ in 7-year-children was seen even in this low exposed population. Given the widespread exposure and increasing use of insecticides, this should be elaborated in future studies.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140618182","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}