Pub Date : 2025-05-01Epub Date: 2025-03-01DOI: 10.1016/j.ntt.2025.107436
Kallio Hunnicutt-Ferguson , Susan A. Stoner , Julie A. Kable , Therese M. Grant , Claire D. Coles
Background
Substance use and mental health problems have been documented in individuals with prenatal alcohol exposure (PAE) in young adulthood, but little is known about how these patterns progress over time into midlife. The current study examined rates of substance use in a sample of adults with PAE in mid-life compared to a demographically similar contrast group.
Methods
Participants (n = 233) were drawn from two longitudinal cohorts of individuals recruited prenatally and followed into adulthood. Measures of cognition, substance use, and self-reported mental health functioning were obtained.
Results
Differences among groups (PAE no dysmorphology, PAE with dysmorphology, No PAE contrast group) were examined on demographic variables of interest and substance use outcomes. Both PAE groups experienced higher levels of Adverse Childhood Experiences (ACEs) compared to the contrast group. We also observed higher rates of current tobacco use in those with PAE; those with PAE and no dysmorphology had almost twice the rate of current tobacco use as the nonexposed contrast group. We observed similar rates of high risk drinking on the Alcohol Use Identification Test (AUDIT) in all groups. Individuals with PAE also showed high rates of cannabis use compared to national averages. Generalized linear regressions examining predictive effects of PAE on substance use outcomes did not show significant results, though female sex at birth was predictive of current cannabis use. Current alcohol use predicted depression and PTSD symptoms, and significant interactions were observed between PAE group and ACEs on depression, PTSD, anxiety, and psychotic symptoms.
Conclusion
This is one of the only studies to examine rates of alcohol and other substance use among adults in mid-life with PAE. Results suggest that relationships between PAE, substance use, and mental health symptoms are complex, and it will be important for future studies to examine factors associated with high-risk substance use among this vulnerable population.
{"title":"Substance use and mental health symptoms in adults with prenatal alcohol exposure","authors":"Kallio Hunnicutt-Ferguson , Susan A. Stoner , Julie A. Kable , Therese M. Grant , Claire D. Coles","doi":"10.1016/j.ntt.2025.107436","DOIUrl":"10.1016/j.ntt.2025.107436","url":null,"abstract":"<div><h3>Background</h3><div>Substance use and mental health problems have been documented in individuals with prenatal alcohol exposure (PAE) in young adulthood, but little is known about how these patterns progress over time into midlife. The current study examined rates of substance use in a sample of adults with PAE in mid-life compared to a demographically similar contrast group.</div></div><div><h3>Methods</h3><div>Participants (<em>n</em> = 233) were drawn from two longitudinal cohorts of individuals recruited prenatally and followed into adulthood. Measures of cognition, substance use, and self-reported mental health functioning were obtained.</div></div><div><h3>Results</h3><div>Differences among groups (PAE no dysmorphology, PAE with dysmorphology, No PAE contrast group) were examined on demographic variables of interest and substance use outcomes. Both PAE groups experienced higher levels of Adverse Childhood Experiences (ACEs) compared to the contrast group. We also observed higher rates of current tobacco use in those with PAE; those with PAE and no dysmorphology had almost twice the rate of current tobacco use as the nonexposed contrast group. We observed similar rates of high risk drinking on the Alcohol Use Identification Test (AUDIT) in all groups. Individuals with PAE also showed high rates of cannabis use compared to national averages. Generalized linear regressions examining predictive effects of PAE on substance use outcomes did not show significant results, though female sex at birth was predictive of current cannabis use. Current alcohol use predicted depression and PTSD symptoms, and significant interactions were observed between PAE group and ACEs on depression, PTSD, anxiety, and psychotic symptoms.</div></div><div><h3>Conclusion</h3><div>This is one of the only studies to examine rates of alcohol and other substance use among adults in mid-life with PAE. Results suggest that relationships between PAE, substance use, and mental health symptoms are complex, and it will be important for future studies to examine factors associated with high-risk substance use among this vulnerable population.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107436"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542553","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 : 2025-05-01Epub Date: 2025-06-17DOI: 10.1016/j.ntt.2025.107498
June-Yung Kim , Sonia Minnes , Meeyoung O. Min , Liat R. Johnson , Lynn T. Singer
{"title":"Co-occurring substance use and mental health symptoms among prenatally substance-exposed emerging adults","authors":"June-Yung Kim , Sonia Minnes , Meeyoung O. Min , Liat R. Johnson , Lynn T. Singer","doi":"10.1016/j.ntt.2025.107498","DOIUrl":"10.1016/j.ntt.2025.107498","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107498"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296880","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 : 2025-05-01Epub Date: 2025-06-17DOI: 10.1016/j.ntt.2025.107490
Elizabeth Green
{"title":"Regulatory aspects of neurobehavioral testing in alternate animal models","authors":"Elizabeth Green","doi":"10.1016/j.ntt.2025.107490","DOIUrl":"10.1016/j.ntt.2025.107490","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107490"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296971","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 : 2025-05-01Epub Date: 2025-03-27DOI: 10.1016/j.ntt.2025.107449
Katherine L. Guyon-Harris , Regan Carell , Montia D. Brock , Kathryn L. Humphreys , Alissa C. Huth-Bocks
Objective
Understanding parenting strengths and challenges among pregnant people in recovery from opioid use disorder supports effective intervention delivery. How parents think and feel about their child prenatally has implications for postnatal parenting. In our past work, greater use of positive compared to negative or neutral prenatal descriptors of the child during pregnancy was associated with higher sensitivity, warmth, and engagement during caregiver–infant interactions 12-months postpartum. We analyzed descriptions of the child among pregnant people in recovery compared to a non-substance using sample to further our understanding of potential parenting strengths and risks for people in recovery.
Method
Participants included pregnant people (N = 18; M age = 30.06, SD = 3.33) recruited from an outpatient substance use treatment program providing buprenorphine (recovery sample) and a comparison sample of pregnant people (N = 120; M age = 26.16, SD = 5.71) reporting high rates of economic disadvantage and intimate partner violence, but not substance use. Through a semi-structured interview, participants described the personality of the child they were pregnant with in up to five words/phrases. Each description was coded as positive, neutral, or negative.
Results
Participants in the recovery sample used a greater number of positive words on average (M = 3.5, SD = 1.4) relative to the comparison sample (M = 2.7, SD = 1.5; Cohen's d = 0.56, 95 % confidence interval: LL = 0.06, UL = 1.06). Use of negative descriptors was similar across samples.
Conclusions
Assessing how pregnant people in recovery think and feel about their developing fetus is feasible and could create opportunities for engagement in preventive parenting interventions to support healthy conceptualizations of the child.
{"title":"Exploring how pregnant people in recovery from opioid use disorder describe their child during pregnancy","authors":"Katherine L. Guyon-Harris , Regan Carell , Montia D. Brock , Kathryn L. Humphreys , Alissa C. Huth-Bocks","doi":"10.1016/j.ntt.2025.107449","DOIUrl":"10.1016/j.ntt.2025.107449","url":null,"abstract":"<div><h3>Objective</h3><div>Understanding parenting strengths and challenges among pregnant people in recovery from opioid use disorder supports effective intervention delivery. How parents think and feel about their child prenatally has implications for postnatal parenting. In our past work, greater use of positive compared to negative or neutral prenatal descriptors of the child during pregnancy was associated with higher sensitivity, warmth, and engagement during caregiver–infant interactions 12-months postpartum. We analyzed descriptions of the child among pregnant people in recovery compared to a non-substance using sample to further our understanding of potential parenting strengths and risks for people in recovery.</div></div><div><h3>Method</h3><div>Participants included pregnant people (<em>N</em> = 18; M age = 30.06, SD = 3.33) recruited from an outpatient substance use treatment program providing buprenorphine (recovery sample) and a comparison sample of pregnant people (<em>N</em> = 120; M age = 26.16, SD = 5.71) reporting high rates of economic disadvantage and intimate partner violence, but not substance use. Through a semi-structured interview, participants described the personality of the child they were pregnant with in up to five words/phrases. Each description was coded as positive, neutral, or negative.</div></div><div><h3>Results</h3><div>Participants in the recovery sample used a greater number of positive words on average (M = 3.5, SD = 1.4) relative to the comparison sample (M = 2.7, SD = 1.5; Cohen's d = 0.56, 95 % confidence interval: LL = 0.06, UL = 1.06). Use of negative descriptors was similar across samples.</div></div><div><h3>Conclusions</h3><div>Assessing how pregnant people in recovery think and feel about their developing fetus is feasible and could create opportunities for engagement in preventive parenting interventions to support healthy conceptualizations of the child.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107449"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737775","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 : 2025-03-01Epub Date: 2025-01-10DOI: 10.1016/j.ntt.2025.107431
Nicholas Cragoe , Jenna Sprowles , Stephanie M. Eick , Lynn Harvey , Xavier R. Ramirez , Gloria Arroyo Sugg , Rachel Morello-Frosch , Tracey Woodruff , Susan L. Schantz
Background
Exposure to maternal stress and depression during pregnancy can have a marked impact on birth outcomes and child development, escalating the likelihood of preterm birth, lower birth weight, and various domains of physical and neurodevelopment.
Methods
The joint ECHO.CA.IL cohort is comprised of the Chemicals in Our Bodies (CIOB) and Illinois Kids Development Study (IKIDS) prospective cohorts, recruiting pregnant women in San Francisco, CA, and Urbana-Champaign, IL, respectively. Using a combined sample of 428 mother-infant dyads, we examined associations between two prenatal measures of maternal stress (perceived stress (PSS) and stressful events (SLE)), as well as maternal depression, and five domains of neurodevelopment via the Ages & Stages Questionnaire (ASQ) administered at 7.5 months. Linear regression models were adjusted for relevant demographic characteristics and used to identify patterns of association.
Results
CIOB mothers were comparatively racially/ethnically diverse (52 % white, 28 % Asian American/Pacific Islander, 12 % Hispanic), while IKIDS mothers were disproportionately white (80 %). Both cohorts demonstrated high levels of maternal education and were similar in terms of other demographic characteristics. CIOB mothers reported higher levels of stress (e.g., SLE: 49.63 % report ≥1 event) compared to IKIDS mothers (e.g., SLE: 16.34 % report ≥1 event). In adjusted linear models, patterns of association were nearly uniformly negative between stress and ASQ measures, with associations between PSS and fine motor skills (β-0.26, CI = -0.52; 0.00) and SLEs and communication skills (β = −2.9245, CI = -6.1643; 0.3152) showing the strongest associations (p < 0.1). Depression showed no significant or clear pattern of association with ASQ scores.
Conclusion
This study found negative associations between prenatal maternal stress and infant neurodevelopment in the combined ECHO.CA.IL cohort, suggesting that prenatal stress is associated with delayed development of motor and communication skills during infancy. The inconclusive links between maternal depression and ASQ outcomes leave open the question regarding the influence of prenatal depression on early child neurodevelopment.
{"title":"Associations of prenatal maternal psychosocial stress and depression with neurodevelopmental outcomes in 7.5-month-old infants in the ECHO.CA.IL prospective birth cohorts","authors":"Nicholas Cragoe , Jenna Sprowles , Stephanie M. Eick , Lynn Harvey , Xavier R. Ramirez , Gloria Arroyo Sugg , Rachel Morello-Frosch , Tracey Woodruff , Susan L. Schantz","doi":"10.1016/j.ntt.2025.107431","DOIUrl":"10.1016/j.ntt.2025.107431","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to maternal stress and depression during pregnancy can have a marked impact on birth outcomes and child development, escalating the likelihood of preterm birth, lower birth weight, and various domains of physical and neurodevelopment.</div></div><div><h3>Methods</h3><div>The joint ECHO.CA.IL cohort is comprised of the Chemicals in Our Bodies (CIOB) and Illinois Kids Development Study (IKIDS) prospective cohorts, recruiting pregnant women in San Francisco, CA, and Urbana-Champaign, IL, respectively. Using a combined sample of 428 mother-infant dyads, we examined associations between two prenatal measures of maternal stress (perceived stress (PSS) and stressful events (SLE)), as well as maternal depression, and five domains of neurodevelopment via the Ages & Stages Questionnaire (ASQ) administered at 7.5 months. Linear regression models were adjusted for relevant demographic characteristics and used to identify patterns of association.</div></div><div><h3>Results</h3><div>CIOB mothers were comparatively racially/ethnically diverse (52 % white, 28 % Asian American/Pacific Islander, 12 % Hispanic), while IKIDS mothers were disproportionately white (80 %). Both cohorts demonstrated high levels of maternal education and were similar in terms of other demographic characteristics. CIOB mothers reported higher levels of stress (e.g., SLE: 49.63 % report ≥1 event) compared to IKIDS mothers (e.g., SLE: 16.34 % report ≥1 event). In adjusted linear models, patterns of association were nearly uniformly negative between stress and ASQ measures, with associations between PSS and fine motor skills (β-0.26, CI = -0.52; 0.00) and SLEs and communication skills (β = −2.9245, CI = -6.1643; 0.3152) showing the strongest associations (<em>p</em> < 0.1). Depression showed no significant or clear pattern of association with ASQ scores.</div></div><div><h3>Conclusion</h3><div>This study found negative associations between prenatal maternal stress and infant neurodevelopment in the combined ECHO.CA.IL cohort, suggesting that prenatal stress is associated with delayed development of motor and communication skills during infancy. The inconclusive links between maternal depression and ASQ outcomes leave open the question regarding the influence of prenatal depression on early child neurodevelopment.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"108 ","pages":"Article 107431"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971704","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 : 2025-03-01Epub Date: 2025-02-21DOI: 10.1016/j.ntt.2025.107435
Charles V. Vorhees, Adam L. Fritz, Brooke M. Gollaway, Michael T. Williams
The prevalence of attention deficit hyperactivity disorder (ADHD) is 9.8 % in U.S. children. Several variants of Latrophiln-3 (LPHN-3) are associated with ADHD. Using CRISPR/Cas9 we deleted exon 3 in rats to create a global Lphn3 knockout. These rats are hyperactive, startle hyper-reactive, impulsive, and have impaired working, spatial, and egocentric learning and memory. Deltamethrin (DLM) is a widely used pyrethroid insecticide. Several epidemiological studies report an increase in ADHD prevalence in children exposed to pyrethroids. Developmental exposure to DLM in rats results in multiple behavioral deficits. The present experiment tested whether Lphn3 disruption interacts with developmental DLM exposure. Because Lphn3−/− rats are severely impaired, we used Lphn3+/− (Hets) because they have an intermediate phenotype. Rats were treated by gavage once/day from postnatal day 6–20 with DLM resulting in four groups: Lphn3-Het + DLM (1.0 mg/kg), Lphn3-Het + Corn Oil (CO), Lphn3+/+ (wildtype: WT) + DLM, and WT + CO. From 31 litters, 19–27 offspring per genotype per treatment per sex were obtained with not more than 1 rat of each group and sex used from any one litter. Adult offspring were tested for exploration (open-field), 72-h home-cage activity, startle, novel object recognition (NOR), radial water maze (RWM), Morris water maze (MWM), and Cincinnati water maze (CWM). On MWM acquisition trials and the reversal probe trial, Lphn3-Het-DLM rats performed worse than other groups. This group also was impaired learning the CWM. No interactions were found for open-field, home-cage, startle, NOR, or RWM. The results show that the ADHD risk gene Lphn3 in combination with developmental DLM exposure has selective adverse effects compared with either factor alone.
{"title":"Gene × environment interaction between heterozygous deletion of the ADHD risk gene latrophilin-3 (adgrl3) and developmental deltamethrin exposure in Sprague Dawley rats","authors":"Charles V. Vorhees, Adam L. Fritz, Brooke M. Gollaway, Michael T. Williams","doi":"10.1016/j.ntt.2025.107435","DOIUrl":"10.1016/j.ntt.2025.107435","url":null,"abstract":"<div><div>The prevalence of attention deficit hyperactivity disorder (ADHD) is 9.8 % in U.S. children. Several variants of <em>Latrophiln-3</em> (<em>LPHN-3</em>) are associated with ADHD. Using CRISPR/Cas9 we deleted exon 3 in rats to create a global <em>Lphn3</em> knockout. These rats are hyperactive, startle hyper-reactive, impulsive, and have impaired working, spatial, and egocentric learning and memory. Deltamethrin (DLM) is a widely used pyrethroid insecticide. Several epidemiological studies report an increase in ADHD prevalence in children exposed to pyrethroids. Developmental exposure to DLM in rats results in multiple behavioral deficits. The present experiment tested whether <em>Lphn3</em> disruption interacts with developmental DLM exposure. Because Lphn3<sup>−/−</sup> rats are severely impaired, we used Lphn3<sup>+/−</sup> (Hets) because they have an intermediate phenotype. Rats were treated by gavage once/day from postnatal day 6–20 with DLM resulting in four groups: <em>Lphn3</em>-Het + DLM (1.0 mg/kg), <em>Lphn3</em>-Het + Corn Oil (CO), <em>Lphn3</em><sup>+/+</sup> (wildtype: WT) + DLM, and WT + CO. From 31 litters, 19–27 offspring per genotype per treatment per sex were obtained with not more than 1 rat of each group and sex used from any one litter. Adult offspring were tested for exploration (open-field), 72-h home-cage activity, startle, novel object recognition (NOR), radial water maze (RWM), Morris water maze (MWM), and Cincinnati water maze (CWM). On MWM acquisition trials and the reversal probe trial, <em>Lphn3</em>-Het-DLM rats performed worse than other groups. This group also was impaired learning the CWM. No interactions were found for open-field, home-cage, startle, NOR, or RWM. The results show that the ADHD risk gene <em>Lphn3</em> in combination with developmental DLM exposure has selective adverse effects compared with either factor alone.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"108 ","pages":"Article 107435"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483725","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 : 2025-03-01Epub Date: 2025-02-06DOI: 10.1016/j.ntt.2025.107432
Marta Tkachuk, Nataliya Matiytsiv
Synthetiс organophosphates are a large group of chemicals, annually produced by an industry with their further application as oil additives, flame retardants, plasticizers, warfare agents and insecticides for domestic use and in the control of vector-borne diseases. Consequently, organophosphates are often detected in the environment and human samples, which can have adverse effects on ecosystems and human health. This review aimed to summarize recent findings about different aspects of tricresyl phosphate mixture and separate isomers toxicity, including their impact on nervous, endocrine, and reproductive systems studied in animal models or in vitro. We also discuss the underlying molecular and cellular mechanisms involved in these processes, which comprise inhibition of neuropathy target esterase (NTE), overactivation of neuregulin1/ErbB and MAPK signaling pathways, impairment of glutamate signaling as well as interaction with nuclear hormone. Finally, we outline potential therapeutic targets and promising agents as important directions for future research.
{"title":"Tricresylphosphate isomers: A review of toxicity pathways","authors":"Marta Tkachuk, Nataliya Matiytsiv","doi":"10.1016/j.ntt.2025.107432","DOIUrl":"10.1016/j.ntt.2025.107432","url":null,"abstract":"<div><div>Synthetiс organophosphates are a large group of chemicals, annually produced by an industry with their further application as oil additives, flame retardants, plasticizers, warfare agents and insecticides for domestic use and in the control of vector-borne diseases. Consequently, organophosphates are often detected in the environment and human samples, which can have adverse effects on ecosystems and human health. This review aimed to summarize recent findings about different aspects of tricresyl phosphate mixture and separate isomers toxicity, including their impact on nervous, endocrine, and reproductive systems studied in animal models or <em>in vitro</em>. We also discuss the underlying molecular and cellular mechanisms involved in these processes, which comprise inhibition of neuropathy target esterase (NTE), overactivation of neuregulin1/ErbB and MAPK signaling pathways, impairment of glutamate signaling as well as interaction with nuclear hormone. Finally, we outline potential therapeutic targets and promising agents as important directions for future research.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"108 ","pages":"Article 107432"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374166","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 : 2025-03-01Epub Date: 2025-02-14DOI: 10.1016/j.ntt.2025.107434
Sifan Xu , Qi Wang , Yu Qin, Qian Yang, Yang Xu, Zhiming Zhou
Objective
To investigate the anti-apoptosis and anti-ferroptosis effects of dl-3-n-butylphthalide (dl-NBP) on cerebral ischemia-reperfusion injury (CIRI) in rats, and the potential involvement of cysteine-X-cysteine chemokine receptor 4 (CXCR4).
Methods
The differentially expressed genes between healthy people and stroke patients were screened by GEO database. A transient middle cerebral artery occlusion rat model was used to induce CIRI in vivo. Rats were randomly divided into sham group, tMCAO group, and dl-NBP + tMCAO group. The therapeutic effect of dl-NBP in vivo and its effect on apoptosis and ferroptosis in brain tissues were evaluated. An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to simulate CIRI in cultured PC12 cells, and the effects of dl-NBP on apoptosis and ferroptosis were examined. In this model, CXCR4 expression was assessed by western blotting and its involvement in dl-NBP-mediated protection assessed by inhibition with AMD3100.
Results
In the stroke-related GSE22255 and GSE66724 datasets, a total of six genes with increased co-expression were found, including CXCR4. Dl-NBP treatment significantly reduced both the volume of cerebral infarction and the degree of cerebral edema, and improved neurological function in rats. dl-NBP reduced the degree of apoptosis and ferroptosis and alleviated CIRI both in vivo and in vitro. The pro-survival effects of dl-NBP were significantly reversed after CXCR4 inhibition with AMD3100.
Conclusion
Dl-NBP has anti-apoptotic and anti-ferroptotic effects on CIRI both in vivo and in vitro, and this effect is mediated by CXCR4.
目的：探讨dl-3-正丁基酞（dl-NBP）对大鼠脑缺血再灌注损伤（CIRI）的抗凋亡和抗铁凋亡作用及其与半胱氨酸- x -半胱氨酸趋化因子受体4 （CXCR4）的关系。方法：采用GEO数据库筛选健康人与脑卒中患者的差异表达基因。采用一过性大脑中动脉闭塞大鼠模型，在体内诱导CIRI。将大鼠随机分为假手术组、tMCAO组和dl-NBP + tMCAO组。观察dl-NBP在体内的治疗效果及对脑组织凋亡和铁下垂的影响。建立体外氧糖剥夺/再灌注（OGD/R）模型，模拟体外培养PC12细胞的CIRI，观察dl-NBP对细胞凋亡和铁凋亡的影响。在该模型中，通过western blotting评估CXCR4的表达，并通过AMD3100抑制评估其参与dl- nbp介导的保护作用。结果：在卒中相关的GSE22255和GSE66724数据集中，共发现6个共表达增加的基因，其中包括CXCR4。Dl-NBP治疗大鼠脑梗死体积和脑水肿程度均明显减少，神经功能明显改善。dl-NBP在体内和体外均能降低细胞凋亡和铁下垂程度，减轻CIRI。AMD3100抑制CXCR4后，dl-NBP的促生存作用明显逆转。结论：Dl-NBP在体内和体外均对CIRI具有抗凋亡和抗铁沉作用，其作用机制是由CXCR4介导的。
{"title":"Dl-3-n-butylphthalein inhibits neuronal apoptosis and ferroptosis after cerebral ischemia-reperfusion injury in rats by regulating CXCR4","authors":"Sifan Xu , Qi Wang , Yu Qin, Qian Yang, Yang Xu, Zhiming Zhou","doi":"10.1016/j.ntt.2025.107434","DOIUrl":"10.1016/j.ntt.2025.107434","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the anti-apoptosis and anti-ferroptosis effects of dl-3-n-butylphthalide (dl-NBP) on cerebral ischemia-reperfusion injury (CIRI) in rats, and the potential involvement of cysteine-X-cysteine chemokine receptor 4 (CXCR4).</div></div><div><h3>Methods</h3><div>The differentially expressed genes between healthy people and stroke patients were screened by GEO database. A transient middle cerebral artery occlusion rat model was used to induce CIRI in vivo. Rats were randomly divided into sham group, tMCAO group, and dl-NBP + tMCAO group. The therapeutic effect of dl-NBP in vivo and its effect on apoptosis and ferroptosis in brain tissues were evaluated. An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to simulate CIRI in cultured PC12 cells, and the effects of dl-NBP on apoptosis and ferroptosis were examined. In this model, CXCR4 expression was assessed by western blotting and its involvement in dl-NBP-mediated protection assessed by inhibition with AMD3100.</div></div><div><h3>Results</h3><div>In the stroke-related GSE22255 and GSE66724 datasets, a total of six genes with increased co-expression were found, including CXCR4. Dl-NBP treatment significantly reduced both the volume of cerebral infarction and the degree of cerebral edema, and improved neurological function in rats. dl-NBP reduced the degree of apoptosis and ferroptosis and alleviated CIRI both in vivo and in vitro. The pro-survival effects of dl-NBP were significantly reversed after CXCR4 inhibition with AMD3100.</div></div><div><h3>Conclusion</h3><div>Dl-NBP has anti-apoptotic and anti-ferroptotic effects on CIRI both in vivo and in vitro, and this effect is mediated by CXCR4.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"108 ","pages":"Article 107434"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433348","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 : 2025-03-01Epub Date: 2025-02-08DOI: 10.1016/j.ntt.2025.107433
Isabel R. Aks , Herry Patel , William E. Pelham III , Marilyn A. Huestis , Natasha E. Wade
<div><h3>Background</h3><div>Cannabis is one of the most widely used drugs in early adolescence, a crucial time for development. Cannabinoids within the cannabis plant (e.g., delta-9-tetrahydrocannabinol [THC], and cannabidiol [CBD]) are suggested to have a range of health implications. These may differ by sex, given sex differences in the endocannabinoid system (ECS). Yet, how aspects of mental and physical health are related to cannabis use as measured by hair concentrations, both within early adolescence and across sexes, is so far inconclusive.</div></div><div><h3>Methods</h3><div>We analyzed hair toxicology data from three cannabinoid analytes (THC, CBD, and 11-nor-9-carboxy-THC [THCCOOH]) and multiple mental and physical health measures in 9–15 year-old youth (49 % female) from the Adolescent Brain Cognitive Development (ABCD) Study (<em>N</em> = 2262). Two-part linear regression models were fit to assess the effects of cannabis constituent presence, concentrations, and THC concentrations + CBD presence on externalizing and internalizing symptoms, physical and strengthening exercise, asthma presence, and sleep duration. Secondary analyses fit the same models but stratified by sex. Finally, to further characterize these relationships, we conducted two exploratory analyses: we assessed health variables prospectively and concurrently predicting cannabinoid concentrations. False discovery rate corrections were employed for all analyses.</div></div><div><h3>Results</h3><div>In the full sample, greater THC concentrations predicted more frequent strength exercise one year later; greater CBD concentrations predicted fewer strength exercise days; and greater THCCOOH concentrations predicted shorter sleep duration. Among males, cannabinoids differentially predicted exercise days; greater THC and THCCOOH concentrations predicted shorter sleep duration. Among females, greater THC and THCCOOH concentrations predicted strength exercise frequency, and THC concentrations predicted shorter sleep duration. In exploratory models, asthma presence predicted THCCOOH concentration one year later. Concurrently, THC concentration alone and in the presence of CBD predicted both sleep duration and lower exercise days, while THCCOOH concentration predicted lower exercise days, less asthma presence, as well as greater internalizing and externalizing symptoms.</div></div><div><h3>Conclusion</h3><div>In a nationwide study of youth ages 9–15 years old, we found cannabinoid hair concentrations predicted differences in health outcomes a year later, suggesting potential differential mechanisms for THC and CBD effects on health. Furthermore, sex-specific observations in these prospective associations emphasize the importance of considering sex assigned at birth when investigating correlates of cannabis use. Analysis of cannabinoid hair concentrations can reveal key links to mental health, physical activity, and sleep, aiding understanding of complex cannabis effects.</div></d
{"title":"Cannabinoids in hair and their prospective association with mental and physical health outcomes in adolescents","authors":"Isabel R. Aks , Herry Patel , William E. Pelham III , Marilyn A. Huestis , Natasha E. Wade","doi":"10.1016/j.ntt.2025.107433","DOIUrl":"10.1016/j.ntt.2025.107433","url":null,"abstract":"<div><h3>Background</h3><div>Cannabis is one of the most widely used drugs in early adolescence, a crucial time for development. Cannabinoids within the cannabis plant (e.g., delta-9-tetrahydrocannabinol [THC], and cannabidiol [CBD]) are suggested to have a range of health implications. These may differ by sex, given sex differences in the endocannabinoid system (ECS). Yet, how aspects of mental and physical health are related to cannabis use as measured by hair concentrations, both within early adolescence and across sexes, is so far inconclusive.</div></div><div><h3>Methods</h3><div>We analyzed hair toxicology data from three cannabinoid analytes (THC, CBD, and 11-nor-9-carboxy-THC [THCCOOH]) and multiple mental and physical health measures in 9–15 year-old youth (49 % female) from the Adolescent Brain Cognitive Development (ABCD) Study (<em>N</em> = 2262). Two-part linear regression models were fit to assess the effects of cannabis constituent presence, concentrations, and THC concentrations + CBD presence on externalizing and internalizing symptoms, physical and strengthening exercise, asthma presence, and sleep duration. Secondary analyses fit the same models but stratified by sex. Finally, to further characterize these relationships, we conducted two exploratory analyses: we assessed health variables prospectively and concurrently predicting cannabinoid concentrations. False discovery rate corrections were employed for all analyses.</div></div><div><h3>Results</h3><div>In the full sample, greater THC concentrations predicted more frequent strength exercise one year later; greater CBD concentrations predicted fewer strength exercise days; and greater THCCOOH concentrations predicted shorter sleep duration. Among males, cannabinoids differentially predicted exercise days; greater THC and THCCOOH concentrations predicted shorter sleep duration. Among females, greater THC and THCCOOH concentrations predicted strength exercise frequency, and THC concentrations predicted shorter sleep duration. In exploratory models, asthma presence predicted THCCOOH concentration one year later. Concurrently, THC concentration alone and in the presence of CBD predicted both sleep duration and lower exercise days, while THCCOOH concentration predicted lower exercise days, less asthma presence, as well as greater internalizing and externalizing symptoms.</div></div><div><h3>Conclusion</h3><div>In a nationwide study of youth ages 9–15 years old, we found cannabinoid hair concentrations predicted differences in health outcomes a year later, suggesting potential differential mechanisms for THC and CBD effects on health. Furthermore, sex-specific observations in these prospective associations emphasize the importance of considering sex assigned at birth when investigating correlates of cannabis use. Analysis of cannabinoid hair concentrations can reveal key links to mental health, physical activity, and sleep, aiding understanding of complex cannabis effects.</div></d","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"108 ","pages":"Article 107433"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391449","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}
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