Neurotoxicology and teratology最新文献

{"title":"Differences in withdrawal symptoms, microglia activity, and cognitive functioning in rats exposed to continuous low-dose heroin in-utero","authors":"Sara L. Mills-Huffnagle ,&nbsp;Charles N. Zawatsky ,&nbsp;Gjhvona Bryant ,&nbsp;Michael Ebert ,&nbsp;Corinne M. Augusto ,&nbsp;Ann Sipe ,&nbsp;Nelli Horvath ,&nbsp;Jennifer E. Nyland","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":"105 ","pages":"Article 107385"},"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":"Xiaoyu Zhong,&nbsp;Jisui Li,&nbsp;Xiaohong Xu","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":"105 ","pages":"Article 107374"},"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":"104 ","pages":"Article 107368"},"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":"104 ","pages":"Article 107369"},"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":"Yasuaki Tanaka ,&nbsp;Asako Shindo ,&nbsp;Wenjing Dong ,&nbsp;Tatsuro Nakamura ,&nbsp;Kyoko Ogura ,&nbsp;Kei Nomiyama ,&nbsp;Hiroki Teraoka","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":"104 ","pages":"Article 107373"},"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}

{"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 ,&nbsp;E.P. Sellinger ,&nbsp;A.S. Brinks ,&nbsp;J.M. Juraska ,&nbsp;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":"104 ","pages":"Article 107370"},"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}

{"title":"Introduction to “Effects of per- and polyfluoroalkyl substances (PFAS) within a developmental context”","authors":"Helen J.K. Sable ,&nbsp;Francheska M. Merced-Nieves ,&nbsp;Jerrold S. Meyer","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":"104 ","pages":"Article 107372"},"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}

{"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":"104 ","pages":"Article 107371"},"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}

{"title":"The 4th Joint ENTIS-OTIS conference abstracts September 12th–15th 2024, Nyborg, Denmark","authors":"","doi":"10.1016/j.ntt.2024.107359","DOIUrl":"10.1016/j.ntt.2024.107359","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"104 ","pages":"Article 107359"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141951316","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":"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 ,&nbsp;Amirhossein Heidari ,&nbsp;Arman Hajikarim-Hamedani ,&nbsp;Zahra Mousavi ,&nbsp;Ghorbangol Ashabi ,&nbsp;Mitra-Sadat Sadat-Shirazi ,&nbsp;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> &lt; 0.05), while depressive-like behavior rose only in maternal and bi-parental ethanol-exposed offspring (<em>p</em> &lt; 0.01). However, compulsive-like behavior increased in all ethanol-exposed offspring (<em>p</em> &lt; 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> &lt; 0.05) and bi-parental ethanol-exposed offspring (p &lt; 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":"104 ","pages":"Article 107367"},"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}