Neurotoxicology and teratology最新文献

{"title":"Unlocking the epigenome: Stress and exercise induced Bdnf regulation in the prefrontal cortex","authors":"Taylor S. Campbell,&nbsp;Katelyn Donoghue,&nbsp;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":"103 ","pages":"Article 107353"},"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}

{"title":"Prenatal exposure to pyrethroids and chlorpyrifos and IQ in 7-year-old children from the Odense Child Cohort","authors":"Stine Søgaard Normann ,&nbsp;Iben Have Beck ,&nbsp;Flemming Nielsen ,&nbsp;Marianne Skovsager Andersen ,&nbsp;Niels Bilenberg ,&nbsp;Tina Kold Jensen ,&nbsp;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":"103 ","pages":"Article 107352"},"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}

{"title":"Characteristics of women concordant and discordant for urine drug screens for cannabis exposure and self-reported cannabis use during pregnancy","authors":"Ryan Bogdan ,&nbsp;Shelby D. Leverett ,&nbsp;Anna M. Constantino-Petit ,&nbsp;Nicole Lashley-Simms ,&nbsp;David B. Liss ,&nbsp;Emma C. Johnson ,&nbsp;Shannon N. Lenze ,&nbsp;Rachel E. Lean ,&nbsp;Tara A. Smyser ,&nbsp;Ebony B. Carter ,&nbsp;Christopher D. Smyser ,&nbsp;Cynthia E. Rogers ,&nbsp;Arpana Agrawal","doi":"10.1016/j.ntt.2024.107351","DOIUrl":"https://doi.org/10.1016/j.ntt.2024.107351","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Increasing cannabis use among pregnant people and equivocal evidence linking prenatal cannabis exposure to adverse outcomes in offspring highlights the need to understand its potential impact on pregnancy and child outcomes. Assessing cannabis use during pregnancy remains a major challenge with potential influences of stigma on self-report as well as detection limitations of easily collected biological matrices.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;This descriptive study examined the concordance between self-reported (SR) cannabis use and urine drug screen (UDS) detection of cannabis exposure during the first trimester of pregnancy and characterized concordant and discordant groups for sociodemographic factors, modes of use, secondhand exposure to cannabis and tobacco, and alcohol use and cotinine positivity.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;p&gt;The Cannabis Use During Development and Early Life (CUDDEL) Study is an ongoing longitudinal study that recruits pregnant individuals presenting for obstetric care, who report lifetime cannabis use as well as using (&lt;em&gt;n&lt;/em&gt; = 289) or not using cannabis (&lt;em&gt;n&lt;/em&gt; = 169) during pregnancy. During the first trimester pregnancy visit, SR of cannabis use and a UDS for cannabis, other illicit drugs and nicotine are acquired from eligible participants, of whom 333 as of 05/01/2023 had both.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Using available CUDDEL Study data on both SR and UDS (&lt;em&gt;n&lt;/em&gt; = 333; age 26.6 ± 4.7; 88.6% Black; 45.4% below federal poverty threshold; 56.5% with paid employment; 89% with high school education; 22% first pregnancy; 12.3 ± 3.6 weeks gestation), we classified pregnant individuals with SR and UDS data into 4 groups based on concordance (&lt;em&gt;k&lt;/em&gt; = 0.49 [95% C.I. 0.40–0.58]) between SR cannabis use and UDS cannabis detection during the first trimester: 1) SR+/UDS+ (&lt;em&gt;n&lt;/em&gt; = 107); 2) SR-/UDS- (&lt;em&gt;n&lt;/em&gt; = 142); 3) SR+/UDS- (&lt;em&gt;n&lt;/em&gt; = 44); 4) SR-/UDS+ (&lt;em&gt;n&lt;/em&gt; = 40). Those who were SR+/UDS- reported less frequent cannabis use and fewer hours under the influence of cannabis during their pregnancy. Those who were SR-/UDS+ were more likely to have joined the study at a lower gestational age with 62.5% reporting cannabis use during their pregnancy prior to being aware that they were pregnant. Of the 40 SR-/UDS+ women, 14 (i.e., 35%) reported past month secondhand exposure, or blunt usage. In the subset of individuals with SR and UDS available at trimester 2 (&lt;em&gt;N&lt;/em&gt; = 160) and 3 (&lt;em&gt;N&lt;/em&gt; = 140), concordant groups were mostly stable and &gt; 50% of those in the discordant groups became concordant by the second trimester. Classifying individuals as exposed or not exposed who were SR+ and/or UDS+ resulted in minor changes in group status based on self-report at screening.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Overall, there was moderate concordance between SR and UDS for cannabis use/exposure during pregnancy. Instances of SR+/UDS- discordancy may partia","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"103 ","pages":"Article 107351"},"PeriodicalIF":2.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140618284","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":"Exposure to Bisphenol F and Bisphenol S during development induces autism-like endophenotypes in adult Drosophila melanogaster","authors":"Elize A. Santos Musachio ,&nbsp;Stefani da Silva Andrade ,&nbsp;Luana Barreto Meichtry ,&nbsp;Eliana Jardim Fernandes ,&nbsp;Pamela Piardi de Almeida ,&nbsp;Dieniffer Espinosa Janner ,&nbsp;Mustafa Munir Mustafa Dahleh ,&nbsp;Gustavo Petri Guerra ,&nbsp;Marina Prigol","doi":"10.1016/j.ntt.2024.107348","DOIUrl":"10.1016/j.ntt.2024.107348","url":null,"abstract":"<div><p>Bisphenol F (BPF) and Bisphenol S (BPS) are being widely used by the industry with the claim of “safer substances”, even with the scarcity of toxicological studies. Given the etiological gap of autism spectrum disorder (ASD), the environment may be a causal factor, so we investigated whether exposure to BPF and BPS during the developmental period can induce ASD-like modeling in adult flies<em>. Drosophila melanogaster</em> flies were exposed during development (embryonic and larval period) to concentrations of 0.25, 0.5, and 1 mM of BPF and BPS, separately inserted into the food. When they transformed into pupae were transferred to a standard diet, ensuring that the flies (adult stage) did not have contact with bisphenols. Thus, after hatching, consolidated behavioral tests were carried out for studies with ASD-type models in flies. It was observed that 1 mM BPF and BPS caused hyperactivity (evidenced by open-field test, negative geotaxis, increased aggressiveness and reproduction of repetitive behaviors). The flies belonging to the 1 mM groups of BPF and BPS also showed reduced cognitive capacity, elucidated by the learning behavior through aversive stimulus. Within the population dynamics that flies exposed to 1 mM BPF and 0.5 and 1 mM BPS showed a change in social interaction, remaining more distant from each other. Exposure to 1 mM BPF, 0.5 and 1 mM BPS increased brain size and reduced Shank immunoreactivity of adult flies. These findings complement each other and show that exposure to BPF and BPS during the development period can elucidate a model with endophenotypes similar to ASD in adult flies. Furthermore, when analyzing comparatively, BPS demonstrated a greater potential for damage when compared to BPF. Therefore, in general these data sets contradict the idea that these substances can be used freely.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"103 ","pages":"Article 107348"},"PeriodicalIF":2.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330038","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":"Combined and sequential exposure to prenatal second hand smoke and postnatal maternal distress is associated with cingulo-opercular global efficiency and attention problems in school-age children","authors":"Paige B. Greenwood ,&nbsp;Mariah DeSerisy ,&nbsp;Emily Koe ,&nbsp;Elizabeth Rodriguez ,&nbsp;Leilani Salas ,&nbsp;Frederica P. Perera ,&nbsp;Julie Herbstman ,&nbsp;David Pagliaccio ,&nbsp;Amy E. Margolis","doi":"10.1016/j.ntt.2024.107338","DOIUrl":"10.1016/j.ntt.2024.107338","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Prenatal exposure to secondhand (environmental) tobacco smoke (SHS) is associated with adverse neurodevelopmental outcomes, including altered functional activation of cognitive control brain circuitry and increased attention problems in children. Exposure to SHS is more common among Black youth who are also disproportionately exposed to socioeconomic disadvantage and concomitant maternal distress. We examine the combined effects of exposure to prenatal SHS and postnatal maternal distress on the global efficiency (GE) of the brain's cingulo-opercular (CO) and fronto-parietal control (FP) networks in childhood, as well as associated attention problems.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Thirty-two children of non-smoking mothers followed in a prospective longitudinal birth cohort at the Columbia Center for Children's Environmental Health (CCCEH) completed magnetic resonance imaging (MRI) at ages 7–9 years old. GE scores were extracted from general connectivity data collected while children completed the Simon Spatial Incompatibility functional magnetic resonance imaging (fMRI) task. Prenatal SHS was measured using maternal urinary cotinine from the third trimester; postnatal maternal distress was assessed at child age 5 using the Psychiatric Epidemiology Research Interview (PERI-D). The Child Behavior Checklist (CBCL) measured Attention and Attention Deficit Hyperactivity Disorder (ADHD) problems at ages 7–9. Linear regressions examined the interaction between prenatal SHS and postnatal maternal distress on the GE of the CO or FP networks, as well as associations between exposure-related network alterations and attention problems. All models controlled for age, sex, maternal education at prenatal visit, race/ethnicity, global brain correlation, and mean head motion.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The prenatal SHS by postnatal maternal distress interaction term associated with the GE of the CO network (β = 0.673, B&lt;sub&gt;u&lt;/sub&gt; = 0.042, t(22) = 2.427, &lt;em&gt;p&lt;/em&gt; = .024, D = 1.42, 95% CI [0.006, 0.079], but not the FP network (β = 0.138, B&lt;sub&gt;u&lt;/sub&gt; = 0.006, t(22) = 0.434, &lt;em&gt;p&lt;/em&gt; = .668, 95% CI [−0.022, 0.033]). Higher GE of the CO network was associated with more attention problems (β = 0.472, B&lt;sub&gt;u&lt;/sub&gt; = 43.076, t(23) = 2.780, &lt;em&gt;p&lt;/em&gt; = .011, D = 1.74, &lt;em&gt;n&lt;/em&gt; = 31, 95% CI [11.024, 75.128], n = 31) and ADHD risk (β = 0.436, B&lt;sub&gt;u&lt;/sub&gt; = 21.961, t(29) = 2.567, &lt;em&gt;p&lt;/em&gt; = .018, D = 1.81, 95% CI [4.219, 39.703], &lt;em&gt;n&lt;/em&gt; = 30).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;These preliminary findings suggest that sequential prenatal SHS exposure and postnatal maternal distress could alter the efficiency of the CO network and increase risk for downstream attention problems and ADHD. These findings are consistent with prior studies showing that prenatal SHS exposure is associated with altered function of brain regions that support cognitive control and with ADHD problems. Our model also identifies postnatal materna","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107338"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022270","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":"Embryonic exposures to cadmium and PAHs cause long-term and interacting neurobehavioral effects in zebrafish","authors":"Alexandra Stickler ,&nbsp;Andrew B. Hawkey ,&nbsp;Anas Gondal ,&nbsp;Sarabesh Natarajan ,&nbsp;Mikayla Mead ,&nbsp;Edward D. Levin","doi":"10.1016/j.ntt.2024.107339","DOIUrl":"10.1016/j.ntt.2024.107339","url":null,"abstract":"<div><p>Developmental exposure to either polycyclic aromatic hydrocarbons (PAHs) or heavy metals has been shown to cause persisting and overlapping neurobehavioral effects in animal models. However, interactions between these compounds have not been well characterized, despite their co-occurrence in a variety of environmental media. In two companion studies, we examined the effects of developmental exposure to cadmium (Cd) with or without co-exposure to prototypic PAHs benzo[<em>a</em>]pyrene (BaP, Exp. 1) or fluoranthene (FA, Exp. 2) using a developing zebrafish model. Zebrafish embryos were exposed to Cd (0–0.3 μM), BaP (0–3 μM), FA (0–1.0 μM), or binary Cd-PAH mixtures from 5 to 122 h post fertilization (hpf). In Exp. 1, Cd and BaP produced independent effects on an array of outcomes and interacting effects on specific outcomes. Notably, Cd-induced deficits in dark-induced locomotor stimulation were attenuated by BaP co-exposure in the larval motility test and BaP-induced hyperactivity was attenuated by Cd co-exposure in the adolescent novel tank test. Likewise, in Exp. 2, Cd and FA produced both independent and interacting effects. FA-induced increases on adult post-tap activity in the tap startle test were attenuated by co-exposure with Cd. On the predator avoidance test, FA- and 0.3 μM Cd-induced hyperactivity effects were attenuated by their co-exposure. Taken together, these data indicate that while the effects of Cd and these representative PAHs on zebrafish behavior were largely independent of one another, binary mixtures can produce sub-additive effects for some neurobehavioral outcomes and at certain ages. This research emphasizes the need for detailed risk assessments of mixtures containing contaminants of differing classes, and for clarity on the mechanisms which allow cross-class toxicant interactions to occur.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107339"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060070","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":"The impact of prenatal alcohol, synthetic cannabinoid and co-exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood","authors":"Laura C. Ornelas ,&nbsp;Eric W. Fish ,&nbsp;Jacob C. Dooley ,&nbsp;Megan Carroll ,&nbsp;Scott E. Parnell ,&nbsp;Joyce Besheer","doi":"10.1016/j.ntt.2024.107341","DOIUrl":"10.1016/j.ntt.2024.107341","url":null,"abstract":"<div><p>Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood. Importantly, we find that prenatal alcohol exposure (PAE) caused lower baseline corticosterone levels in adolescent males and females. Co-exposure to alcohol + CP produced hyperactivity during open field test in males, but not females. During the two-bottle choice alcohol-drinking procedure, prenatal cannabinoid exposed male and female adolescent rats drank more alcohol than their vehicle-exposed controls. In adulthood, female rats treated with prenatal cannabinoid exposure (PCE), showed an overall total increase in alcohol intake during alcohol self-administration; but this was not found in males. When the reinforcer was changed to a 1% sucrose solution, male rats exposed to PCE, showed a reduced self-administration compared to vehicle-exposed males, potentially indicative of an anhedonic response. This lower self-administration persisted when 20% alcohol was reintroduced to the sucrose solution. Lastly, following an abstinence period, there were no changes due to prenatal drug exposure in either males or females. Overall, these data suggest lasting consequences of prenatal alcohol and cannabinoid exposure during adolescence and adulthood in male and female rats.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107341"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137043","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":"Maternal choline supplementation lessens the behavioral dysfunction produced by developmental manganese exposure in a rodent model of ADHD","authors":"Shanna L. Howard ,&nbsp;Stephane A. Beaudin ,&nbsp;Barbara J. Strupp ,&nbsp;Donald R. Smith","doi":"10.1016/j.ntt.2024.107337","DOIUrl":"10.1016/j.ntt.2024.107337","url":null,"abstract":"<div><p>Studies in children have reported associations between elevated manganese (Mn) exposure and ADHD-related symptoms of inattention, impulsivity/hyperactivity, and psychomotor impairment. Maternal choline supplementation (MCS) during pregnancy/lactation may hold promise as a protective strategy because it has been shown to lessen cognitive dysfunction caused by numerous early insults. Our objectives were to determine whether (1) developmental Mn exposure alters behavioral reactivity/emotion regulation, in addition to impairing learning, attention, impulse control, and sensorimotor function, and (2) MCS protects against these Mn-induced impairments<strong>.</strong> Pregnant Long-Evans rats were given standard diet, or a diet supplemented with additional choline throughout gestation and lactation (GD 3 - PND 21). Male offspring were exposed orally to 0 or 50 mg Mn/kg/day over PND 1–21. In adulthood, animals were tested in a series of learning, attention, impulse control, and sensorimotor tasks. Mn exposure caused lasting dysfunction in attention, reactivity to errors and reward omission, learning, and sensorimotor function, recapitulating the constellation of symptoms seen in ADHD children. MCS lessened Mn-induced attentional dysfunction and partially normalized reactivity to committing an error or not receiving an expected reward but provided no protection against Mn-induced learning or sensorimotor dysfunction. In the absence of Mn exposure, MCS produces lasting offspring benefits in learning, attention, and reactivity to errors. To conclude, developmental Mn exposure produces a constellation of deficits consistent with ADHD symptomology, and MCS offered some protection against the adverse Mn effects, adding to the evidence that maternal choline supplementation is neuroprotective for offspring and improves offspring cognitive functioning.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107337"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996968","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":"The association between prenatal cannabis use and congenital birth defects in offspring: A cumulative meta-analysis","authors":"Abay Woday Tadesse ,&nbsp;Getinet Ayano ,&nbsp;Berihun Assefa Dachew ,&nbsp;Biruk Shalmeno Tusa ,&nbsp;Yitayish Damtie ,&nbsp;Kim Betts ,&nbsp;Rosa Alati","doi":"10.1016/j.ntt.2024.107340","DOIUrl":"10.1016/j.ntt.2024.107340","url":null,"abstract":"<div><h3>Objective</h3><p>To examine the association between prenatal cannabis use and structural birth defects in exposed offspring.</p></div><div><h3>Methods</h3><p>In line with the preregistered protocol (PROSPERO: CRD42022368623), we systematically searched PubMed/Medline, CINHAL, EMBASE, Web of Science, ProQuest, Psych-Info, and Google Scholar for published articles until 25 January 2024. The methodological quality of the included studies was appraised by the Newcastle-Ottawa Quality Assessment Scale (NOS). A meta-analysis was carried out to report the pooled effect estimates from the included studies. We further performed subgroup, leave-one-out sensitivity, and meta-regression analyses, which increased the robustness of our findings.</p></div><div><h3>Results</h3><p>In this cumulative meta-analysis, thirty-six observational studies, consisting of 18 case-control and 18 cohort studies, with 230, 816 cases of birth defects and 18,049,013 controls (healthy babies) were included in the final analysis. We found that offspring exposed to maternal prenatal cannabis are at greater risks of a wide range of structural birth defects: cardiovascular/heart [OR = 2.35: 95 % CI 1.63 – 3.39], gastrointestinal [OR = 2.42: 95 % CI 1.61 – 3.64], central nervous system [OR = 2.87: 95 % CI 1.51 – 5.46], genitourinary [OR = 2.39: 95 % CI 1.11 – 5.17], and any (unclassified) birth defects [OR = 1.25: 95 % CI 1.12 – 1.41].</p></div><div><h3>Conclusion</h3><p>The findings from the current study suggest that maternal prenatal cannabis exposure is associated with a higher risk of different forms of structural birth defects in offspring. The findings underscore the significance of implementing preventive strategies, including enhanced preconception counselling, to address cannabis use during pregnancy and mitigate the risk of birth defects in offspring.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107340"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068606","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":"A novel deep learning-based method for automatic stereology of microglia cells from low magnification images","authors":"Hunter Morera ,&nbsp;Palak Dave ,&nbsp;Yaroslav Kolinko ,&nbsp;Saeed Alahmari ,&nbsp;Aidan Anderson ,&nbsp;Grant Denham ,&nbsp;Chloe Davis ,&nbsp;Juan Riano ,&nbsp;Dmitry Goldgof ,&nbsp;Lawrence O. Hall ,&nbsp;G. Jean Harry ,&nbsp;Peter R. Mouton","doi":"10.1016/j.ntt.2024.107336","DOIUrl":"10.1016/j.ntt.2024.107336","url":null,"abstract":"<div><p>Microglial cells mediate diverse homeostatic, inflammatory, and immune processes during normal development and in response to cytotoxic challenges. During these functional activities, microglial cells undergo distinct numerical and morphological changes in different tissue volumes in both rodent and human brains. However, it remains unclear how these cytostructural changes in microglia correlate with region-specific neurochemical functions. To better understand these relationships, neuroscientists need accurate, reproducible, and efficient methods for quantifying microglial cell number and morphologies in histological sections. To address this deficit, we developed a novel deep learning (DL)-based classification, stereology approach that links the appearance of Iba1 immunostained microglial cells at low magnification (20×) with the total number of cells in the same brain region based on unbiased stereology counts as ground truth. Once DL models are trained, total microglial cell numbers in specific regions of interest can be estimated and treatment groups predicted in a high-throughput manner (&lt;1 min) using only low-power images from test cases, without the need for time and labor-intensive stereology counts or morphology ratings in test cases. Results for this DL-based automatic stereology approach on two datasets (total 39 mouse brains) showed &gt;90% accuracy, 100% percent repeatability (Test-Retest) and 60× greater efficiency than manual stereology (&lt;1 min vs. ∼ 60 min) using the same tissue sections. Ongoing and future work includes use of this DL-based approach to establish clear neurodegeneration profiles in age-related human neurological diseases and related animal models.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107336"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139954523","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}