Pub Date : 2025-04-17DOI: 10.1016/j.neuro.2025.04.007
Diego Ruiz-Sobremazas , Mario Coca , Miguel Morales-Navas , Rocío Rodulfo-Cardenas , Caridad Lopez-Granero , Maria-Teresa Colomina , Cristian Perez-Fernandez , Fernando Sanchez-Santed
Air pollutants have been associated with various neurodevelopmental disorders, with several studies specifically linking Particulate Matter (PM) exposure to attentional and social deficits. This link is even more pronounced when exposure occurs during the prenatal period, as it can disrupt normal brain development. However, while social deficits have been extensively studied during adolescence, their impact on adult social behaviors remains largely unexplored. To investigate these effects, pregnant Wistar rats were exposed throughout gestation (GD1-GD21) to PM10 at a dosage of 200 μg/Kg/day diluted in PBS that was freely drunk. After birth, the pups were evaluated on developmental milestones such as weight progression, ocular opening, and muscular strength. In adulthood, inhibitory control was assessed using the Five Choice Serial Reaction Time Task (5-CSRTT), social behavior using the Three-Chambered Crawley’s Test (3-CT), and object recognition using the Novelty Object Recognition test (NOR). The results indicated that prenatal PM10 exposure is associated with higher birth weight and poorer performance in neuromuscular tests. However, no significant differences were observed in inhibitory control (5-CSRTT) or social behavior (3-CT). Interestingly, prenatally exposed rodents showed heightened novelty responses in the NOR test. In conclusion, gestational exposure to PM10 is related to differences in neurodevelopmental milestones, including weight and muscular strength. While it does not impact adult inhibitory control or social behavior, it influences novelty recognition in later life.
{"title":"The effects of oral gestational particulate matter 10 exposure: Insights into neurodevelopmental milestones, inhibitory control, adult sociability, and object recognition","authors":"Diego Ruiz-Sobremazas , Mario Coca , Miguel Morales-Navas , Rocío Rodulfo-Cardenas , Caridad Lopez-Granero , Maria-Teresa Colomina , Cristian Perez-Fernandez , Fernando Sanchez-Santed","doi":"10.1016/j.neuro.2025.04.007","DOIUrl":"10.1016/j.neuro.2025.04.007","url":null,"abstract":"<div><div>Air pollutants have been associated with various neurodevelopmental disorders, with several studies specifically linking Particulate Matter (PM) exposure to attentional and social deficits. This link is even more pronounced when exposure occurs during the prenatal period, as it can disrupt normal brain development. However, while social deficits have been extensively studied during adolescence, their impact on adult social behaviors remains largely unexplored. To investigate these effects, pregnant Wistar rats were exposed throughout gestation (GD1-GD21) to PM<sub>10</sub> at a dosage of 200 μg/Kg/day diluted in PBS that was freely drunk. After birth, the pups were evaluated on developmental milestones such as weight progression, ocular opening, and muscular strength. In adulthood, inhibitory control was assessed using the Five Choice Serial Reaction Time Task (5-CSRTT), social behavior using the Three-Chambered Crawley’s Test (3-CT), and object recognition using the Novelty Object Recognition test (NOR). The results indicated that prenatal PM10 exposure is associated with higher birth weight and poorer performance in neuromuscular tests. However, no significant differences were observed in inhibitory control (5-CSRTT) or social behavior (3-CT). Interestingly, prenatally exposed rodents showed heightened novelty responses in the NOR test. In conclusion, gestational exposure to PM<sub>10</sub> is related to differences in neurodevelopmental milestones, including weight and muscular strength. While it does not impact adult inhibitory control or social behavior, it influences novelty recognition in later life.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 231-245"},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855225","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 : 2025-04-14DOI: 10.1016/j.neuro.2025.04.006
Ismail Bolat , Serkan Yildirim , Yavuz Selim Saglam , Selim Comakli , Samet Teki̇n , Merve Bolat , Tuba Dogan , Metin Ki̇li̇cli̇oglu , Berrah Gozegi̇r
Cadmium (Cd) is a naturally occurring harmful metal that can cause damage to many different tissues and organs in the body. Antioxidant agents are frequently utilized to counteract the harmful impact of this heavy metal on the body. This research explores the neuroprotective role of β-caryophyllene (BCP) in Cd-induced toxicity. Male Wistar rats were categorized into five groups: control, BCP400, Cd, BCP200 +Cd, and BCP400 +Cd. BCP suppressed Cd-induced oxidative damage in brain tissue by regulating the Nrf2/HO-1/SIRT1 signaling pathway. Moreover, BCP alleviates Cd-induced behavioral alterations through SIRT1 activation. Cd increased TNF-α and IL-1β levels and decreased IL-10 levels in brain tissue, whereas BCP suppressed TLR-4/NF-κB/JNK signaling pathway and restored these cytokines to normal levels. In addition, Cd exposure led to increased BAX and Caspase 3 and decreased Bcl-2 levels in neurons, but these proteins approached normal levels thanks to BCP's anti-apoptotic properties. Furthermore, while Beclin-1 and LC3A/B expression levels were increased in neurons of Cd-exposed animals, BCP suppressed these expressions by activating the PI3K/Akt/mTOR signaling pathway. Histopathological, biochemical, and molecular analyses confirmed BCP reduces oxidative stress, inflammation, apoptosis, and autophagy caused by Cd-induced neurotoxicity by regulating various signaling pathways and strengthening the antioxidant defense system. Therefore, we believe that BCP has a high potential as a therapeutic agent against Cd-induced neurotoxicity.
{"title":"β-Caryophyllene attenuates cadmium induced neurotoxicity in rats by modulating different cellular signaling pathways","authors":"Ismail Bolat , Serkan Yildirim , Yavuz Selim Saglam , Selim Comakli , Samet Teki̇n , Merve Bolat , Tuba Dogan , Metin Ki̇li̇cli̇oglu , Berrah Gozegi̇r","doi":"10.1016/j.neuro.2025.04.006","DOIUrl":"10.1016/j.neuro.2025.04.006","url":null,"abstract":"<div><div>Cadmium (Cd) is a naturally occurring harmful metal that can cause damage to many different tissues and organs in the body. Antioxidant agents are frequently utilized to counteract the harmful impact of this heavy metal on the body. This research explores the neuroprotective role of β-caryophyllene (BCP) in Cd-induced toxicity. Male Wistar rats were categorized into five groups: control, BCP400, Cd, BCP200 +Cd, and BCP400 +Cd. BCP suppressed Cd-induced oxidative damage in brain tissue by regulating the Nrf2/HO-1/SIRT1 signaling pathway. Moreover, BCP alleviates Cd-induced behavioral alterations through SIRT1 activation<del>.</del> Cd increased TNF-α and IL-1β levels and decreased IL-10 levels in brain tissue, whereas BCP suppressed TLR-4/NF-κB/JNK signaling pathway and restored these cytokines to normal levels. In addition, Cd exposure led to increased BAX and Caspase 3 and decreased Bcl-2 levels in neurons, but these proteins approached normal levels thanks to BCP's anti-apoptotic properties. Furthermore, while Beclin-1 and LC3A/B expression levels were increased in neurons of Cd-exposed animals, BCP suppressed these expressions by activating the PI3K/Akt/mTOR signaling pathway. Histopathological, biochemical, and molecular analyses confirmed BCP reduces oxidative stress, inflammation, apoptosis, and autophagy caused by Cd-induced neurotoxicity by regulating various signaling pathways and strengthening the antioxidant defense system. Therefore, we believe that BCP has a high potential as a therapeutic agent against Cd-induced neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 206-217"},"PeriodicalIF":3.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833852","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 : 2025-04-12DOI: 10.1016/j.neuro.2025.04.005
Surekha Ramachandran , Sumathi Thangarajan
3-Nitropropionic acid (3-NP) is a mitochondrial toxin which causes bilateral striatal lesions in experimental animals, mimicking Huntington’s disease (HD) pathology. The molecular mechanisms underlying 3-NP-induced neuronal death involve mitochondrial dysfunction, transcriptional dysregulation, and impaired antioxidant defense systems. This study investigated the effects of thymoquinone (TQ) encapsulated in solid lipid nanoparticles (NanoTQ), on mitochondrial biogenesis in 3-NP-induced neurotoxicity in the striatum of male Wistar rats. Systemic administration of 3-NP (10 mg/kg) for 14 days inhibited mitochondrial complex enzymes and increased mitochondrial membrane permeability in the striatum. 3-NP exposure significantly altered the translational level of PGC-1α by modifying the expression of p-CREB/TORC1/SIRT1/PPARγ. Additionally, 3-NP exposure significantly reduced striatal levels of BDNF, GDNF, and their downstream effectors. Treatment with NanoTQ (10 and 20 mg/kg) and TQ (80 mg/kg) significantly (P < 0.01) increased mitochondrial complex enzyme activity compared to TQ (40 mg/kg). NanoTQ also significantly (P < 0.01) regulated the expression of regulatory proteins, promoting PGC-1α mediated mitochondrial biogenesis. Furthermore, NanoTQ restored BDNF and GDNF signaling and enhanced the antioxidant defense mechanism by increasing Nrf-2 and HO-1 expression while reducing Keap1 levels in the striatum. In conclusion, NanoTQ effectively mitigated 3-NP-induced neurotoxicity by regulating the mitochondrial biogenesis, neurotrophic factors, and antioxidant defense system, thereby preventing HD-like symptoms in rats.
{"title":"Thymoquinone-loaded solid lipid nanoparticles mitigate 3-Nitropropionic acid-induced mitochondrial dysfunction and oxidative damage via regulating PGC-1α/Nrf2 pathway","authors":"Surekha Ramachandran , Sumathi Thangarajan","doi":"10.1016/j.neuro.2025.04.005","DOIUrl":"10.1016/j.neuro.2025.04.005","url":null,"abstract":"<div><div>3-Nitropropionic acid (3-NP) is a mitochondrial toxin which causes bilateral striatal lesions in experimental animals, mimicking Huntington’s disease (HD) pathology. The molecular mechanisms underlying 3-NP-induced neuronal death involve mitochondrial dysfunction, transcriptional dysregulation, and impaired antioxidant defense systems. This study investigated the effects of thymoquinone (TQ) encapsulated in solid lipid nanoparticles (NanoTQ), on mitochondrial biogenesis in 3-NP-induced neurotoxicity in the striatum of male Wistar rats. Systemic administration of 3-NP (10 mg/kg) for 14 days inhibited mitochondrial complex enzymes and increased mitochondrial membrane permeability in the striatum. 3-NP exposure significantly altered the translational level of PGC-1α by modifying the expression of p-CREB/TORC1/SIRT1/PPARγ. Additionally, 3-NP exposure significantly reduced striatal levels of BDNF, GDNF, and their downstream effectors. Treatment with NanoTQ (10 and 20 mg/kg) and TQ (80 mg/kg) significantly (<em>P</em> < 0.01) increased mitochondrial complex enzyme activity compared to TQ (40 mg/kg). NanoTQ also significantly (<em>P</em> < 0.01) regulated the expression of regulatory proteins, promoting PGC-1α mediated mitochondrial biogenesis. Furthermore, NanoTQ restored BDNF and GDNF signaling and enhanced the antioxidant defense mechanism by increasing Nrf-2 and HO-1 expression while reducing Keap1 levels in the striatum. In conclusion, NanoTQ effectively mitigated 3-NP-induced neurotoxicity by regulating the mitochondrial biogenesis, neurotrophic factors, and antioxidant defense system, thereby preventing HD-like symptoms in rats.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 191-205"},"PeriodicalIF":3.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829881","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 : 2025-04-11DOI: 10.1016/j.neuro.2025.04.001
Gillian England-Mason , Sarah J. MacEachern , Kimberly Amador , Munawar Hussain Soomro , Anthony J.F. Reardon , Amy M. MacDonald , David W. Kinniburgh , Nicole Letourneau , Gerald F. Giesbrecht , Jonathan W. Martin , Nils D. Forkert , Deborah Dewey
Research investigating the prenatal chemical exposome and child neurodevelopment has typically focused on a limited number of chemical exposures and controlled for sociodemographic factors and maternal mental health. Emerging machine learning approaches may facilitate more comprehensive examinations of the contributions of chemical exposures, sociodemographic factors, and maternal mental health to child neurodevelopment. A machine learning pipeline that utilized feature selection and ranking was applied to investigate which common prenatal chemical exposures and sociodemographic factors best predict neurodevelopmental outcomes in young children. Data from 406 maternal-child pairs enrolled in the APrON study were used. Maternal concentrations of 32 environmental chemical exposures (i.e., phthalates, bisphenols, per- and polyfluoroalkyl substances (PFAS), metals, trace elements) measured during pregnancy and 11 sociodemographic factors, as well as measures of maternal mental health and urinary creatinine were entered into the machine learning pipeline. The pipeline, which consisted of a RReliefF variable selection algorithm and support vector machine regression model, was used to identify and rank the best subset of variables predictive of cognitive, language, and motor development outcomes on the Bayley Scales of Infant Development-Third Edition (Bayley-III) at 2 years of age. Bayley-III cognitive scores were best predicted using 29 variables, resulting in a correlation coefficient of r = 0.27 (R2=0.07). For language outcomes, 45 variables led to the best result (r = 0.30; R2=0.09), whereas for motor outcomes 33 variables led to the best result (r = 0.28, R2=0.09). Environmental chemicals, sociodemographic factors, and maternal mental health were found to be highly ranked predictors of cognitive, language, and motor development in young children. Our findings demonstrate the potential of machine learning approaches to identify and determine the relative importance of different predictors of child neurodevelopmental outcomes. Future developmental neurotoxicology research should consider the prenatal chemical exposome as well as sample characteristics such as sociodemographic factors and maternal mental health as important predictors of child neurodevelopment.
{"title":"Using machine learning to investigate the influence of the prenatal chemical exposome on neurodevelopment of young children","authors":"Gillian England-Mason , Sarah J. MacEachern , Kimberly Amador , Munawar Hussain Soomro , Anthony J.F. Reardon , Amy M. MacDonald , David W. Kinniburgh , Nicole Letourneau , Gerald F. Giesbrecht , Jonathan W. Martin , Nils D. Forkert , Deborah Dewey","doi":"10.1016/j.neuro.2025.04.001","DOIUrl":"10.1016/j.neuro.2025.04.001","url":null,"abstract":"<div><div>Research investigating the prenatal chemical exposome and child neurodevelopment has typically focused on a limited number of chemical exposures and controlled for sociodemographic factors and maternal mental health. Emerging machine learning approaches may facilitate more comprehensive examinations of the contributions of chemical exposures, sociodemographic factors, and maternal mental health to child neurodevelopment. A machine learning pipeline that utilized feature selection and ranking was applied to investigate which common prenatal chemical exposures and sociodemographic factors best predict neurodevelopmental outcomes in young children. Data from 406 maternal-child pairs enrolled in the APrON study were used. Maternal concentrations of 32 environmental chemical exposures (<em>i.e.,</em> phthalates, bisphenols, per- and polyfluoroalkyl substances (PFAS), metals, trace elements) measured during pregnancy and 11 sociodemographic factors, as well as measures of maternal mental health and urinary creatinine were entered into the machine learning pipeline. The pipeline, which consisted of a RReliefF variable selection algorithm and support vector machine regression model, was used to identify and rank the best subset of variables predictive of cognitive, language, and motor development outcomes on the Bayley Scales of Infant Development-Third Edition (Bayley-III) at 2 years of age. Bayley-III cognitive scores were best predicted using 29 variables, resulting in a correlation coefficient of r = 0.27 (R<sup>2</sup>=0.07). For language outcomes, 45 variables led to the best result (r = 0.30; R<sup>2</sup>=0.09), whereas for motor outcomes 33 variables led to the best result (r = 0.28, R<sup>2</sup>=0.09). Environmental chemicals, sociodemographic factors, and maternal mental health were found to be highly ranked predictors of cognitive, language, and motor development in young children. Our findings demonstrate the potential of machine learning approaches to identify and determine the relative importance of different predictors of child neurodevelopmental outcomes. Future developmental neurotoxicology research should consider the prenatal chemical exposome as well as sample characteristics such as sociodemographic factors and maternal mental health as important predictors of child neurodevelopment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 218-230"},"PeriodicalIF":3.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844953","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}
Cannabis sativa L. presents a very complex composition that includes several secondary metabolites besides the two main compounds, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Many of these minor cannabinoids are still under investigation and are arousing increasing interest for their biological effects and potential therapeutic roles. Cannabis sativa extracts, either properly purified and enriched with cannabinoids, were tested here on the neuronal activity, by monitoring the spontaneous firing rate and the bursts generation of cultured hippocampal neurons. In particular, we focused on the combined effect of THC, CBD and cannabidivarin (CBDV), a non-psychoactive homologue of CBD whose side chain has two fewer carbon atoms, and their related standard compounds. We found that standard THC, recognised for its psychoactive impact and side effects including anxiety and paranoia, significantly decreased the spontaneous firing discharge of cultured hippocampal neurons, whether applied alone or in combination with standard CBD at comparable concentrations. In contrast, the firing activity did not exhibit any significant alterations when CBD was administered alone. When C. sativa extracts were tested, we found that CBDV was able to reverse the inhibition of the firing discharge caused by the mixture of THC and CBD. Furthermore, when administered alone, CBDV significantly increased the firing discharge of hippocampal neurons. In all tested conditions, the effects exerted by standard compounds or extracts were restored to control conditions after 24 hours from administration. Overall, these data unravel a novel action of CBDV in reverting the detrimental effect exerted by the THC+CBD on neuronal firing activity.
{"title":"THC, CBD and minor cannabinoid CBDV differently modulate hippocampal neurons firing","authors":"Giulia Tomagra , Nikita Gandlevskiy , Elena Rosso , Monica Bonardi , Arianna Binello , Valentina Carabelli , Alessandro Barge","doi":"10.1016/j.neuro.2025.04.004","DOIUrl":"10.1016/j.neuro.2025.04.004","url":null,"abstract":"<div><div><em>Cannabis sativa</em> L. presents a very complex composition that includes several secondary metabolites besides the two main compounds, Δ<sup>9</sup>-tetrahydrocannabinol (THC) and cannabidiol (CBD). Many of these minor cannabinoids are still under investigation and are arousing increasing interest for their biological effects and potential therapeutic roles. <em>Cannabis sativa</em> extracts, either properly purified and enriched with cannabinoids, were tested here on the neuronal activity, by monitoring the spontaneous firing rate and the bursts generation of cultured hippocampal neurons. In particular, we focused on the combined effect of THC, CBD and cannabidivarin (CBDV), a non-psychoactive homologue of CBD whose side chain has two fewer carbon atoms, and their related standard compounds. We found that standard THC, recognised for its psychoactive impact and side effects including anxiety and paranoia, significantly decreased the spontaneous firing discharge of cultured hippocampal neurons, whether applied alone or in combination with standard CBD at comparable concentrations. In contrast, the firing activity did not exhibit any significant alterations when CBD was administered alone. When <em>C. sativa</em> extracts were tested, we found that CBDV was able to reverse the inhibition of the firing discharge caused by the mixture of THC and CBD. Furthermore, when administered alone, CBDV significantly increased the firing discharge of hippocampal neurons. In all tested conditions, the effects exerted by standard compounds or extracts were restored to control conditions after 24 hours from administration. Overall, these data unravel a novel action of CBDV in reverting the detrimental effect exerted by the THC+CBD on neuronal firing activity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 180-190"},"PeriodicalIF":3.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815007","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 : 2025-04-05DOI: 10.1016/j.neuro.2025.03.009
Gabriel Barg , Juan Andrés Menéndez , Juan Andrés Friedl , Sandra Hoyos , Elena I. Queirolo , Nelly Mañay , Diala Ghazal , Katarzyna Kordas
Introduction
Lead exposure has been linked to significant brain disruptions. However, research on the neural correlates of blood lead level (BLL) and cognitive control remains limited. To address this gap, we investigated event-related potentials (ERPs) during an inhibition task, in conjunction with measurements of serum neurotransmitter availability.
Method
38 children (58 % girls) aged 9–13 years were evaluated using a go/no-go task. Total hits, commission and omission errors were registered. During the task, ERPs were recorded using a 59-channel array. BLL was measured using atomic absorption via flame or graphite furnace ionization techniques. In an exploratory approach, serum level of neurochemical factors such as BDNF, dopamine, serotonin, and GABA in serum were assessed using enzyme-linked immunosorbent assays.
Results
Median BLL was 1.00 µg/dL (IQR = 0.7, 1.7). In generalized linear regression models with Poisson distribution, BLL was associated with a 23 % higher commission errors (IRR [95 % CI] = 1.23 [1.14, 1.34]) and 16 % (1.16 [1.08, 1.22]) total omission errors after adjustment for age, sex, maternal education and hemoglobin level. Two ERPs linked to conflict monitoring (N2) and response inhibition (P3) showed positive, although non-significant, modulation by BLL. Regarding the neurotransmitters, dopamine was correlated with BLL particularly when measured concurrently (Spearman's rho = 0.51, p < 0.005)
Conclusions
BLL are associated with deficits in the inhibition of prepotent responses during pre-adolescence. Such failures can hinder academic and social development and increase risky behaviors. This study is the first to examine peripheral neurotransmitter levels and brain activity associated with cognitive control in Pb-exposed children.
{"title":"Lead exposure, peripheral neurotransmitter levels and cognitive control: A neurobehavioral study in children from Montevideo, Uruguay","authors":"Gabriel Barg , Juan Andrés Menéndez , Juan Andrés Friedl , Sandra Hoyos , Elena I. Queirolo , Nelly Mañay , Diala Ghazal , Katarzyna Kordas","doi":"10.1016/j.neuro.2025.03.009","DOIUrl":"10.1016/j.neuro.2025.03.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Lead exposure has been linked to significant brain disruptions. However, research on the neural correlates of blood lead level (BLL) and cognitive control remains limited. To address this gap, we investigated event-related potentials (ERPs) during an inhibition task, in conjunction with measurements of serum neurotransmitter availability.</div></div><div><h3>Method</h3><div>38 children (58 % girls) aged 9–13 years were evaluated using a go/no-go task. Total hits, commission and omission errors were registered. During the task, ERPs were recorded using a 59-channel array. BLL was measured using atomic absorption via flame or graphite furnace ionization techniques. In an exploratory approach, serum level of neurochemical factors such as BDNF, dopamine, serotonin, and GABA in serum were assessed using enzyme-linked immunosorbent assays.</div></div><div><h3>Results</h3><div>Median BLL was 1.00 µg/dL (IQR = 0.7, 1.7). In generalized linear regression models with Poisson distribution, BLL was associated with a 23 % higher commission errors (IRR [95 % CI] = 1.23 [1.14, 1.34]) and 16 % (1.16 [1.08, 1.22]) total omission errors after adjustment for age, sex, maternal education and hemoglobin level. Two ERPs linked to conflict monitoring (N2) and response inhibition (P3) showed positive, although non-significant, modulation by BLL. Regarding the neurotransmitters, dopamine was correlated with BLL particularly when measured concurrently (Spearman's rho = 0.51, p < 0.005)</div></div><div><h3>Conclusions</h3><div>BLL are associated with deficits in the inhibition of prepotent responses during pre-adolescence. Such failures can hinder academic and social development and increase risky behaviors. This study is the first to examine peripheral neurotransmitter levels and brain activity associated with cognitive control in Pb-exposed children.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 159-168"},"PeriodicalIF":3.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796025","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 : 2025-04-04DOI: 10.1016/j.neuro.2025.04.003
Dong-Xue Fu , Ya-Ting Lei , Hai-Bo Guo , Ting Chen , Xiang-Ying Gao , Xiao-Li Wang , Xiang Huang , Ling-Ling Song , Sheng-Yuan Wang , Qin-Xue Dai
Peroxiredoxin 1 (PRDX1) is a member of the peroxidase family of antioxidant enzymes. However, the role and mechanism of PRDX1 in acrylamide (ACR)-induced nerve damage have not been reported. We used SD rats and well-differentiated rat pheochromocytoma cells (PC-12 cells) to established in vivo and in vitro models of ACR. Immunohistochemistry, immunofluorescence and RT-qPCR experiments were used to detect the expression of PRDX1 in neurons of rat hippocampal tissue. The ultrastructural changes of neurons and PC-12 cells in rat hippocampal tissue were observed under transmission electron microscope. Western blot detected the protein expression levels of PRDX1, PTEN, AKT and p-AKT. In vivo and in vitro experimental results showed that PRDX1 showed a significant up-regulation trend after ACR exposure (p < 0.05). In vitro experiments showed that after inhibiting PRDX1 expression with PRDX1 siRNA, the survival rate of PC-12 cells significantly increased, and the damage to cell morphology and organelles was markedly improved. Western blot analysis revealed that ACR exposure can cause a significant increase in PTEN protein expression level and p-AKT/AKT protein ratio (p < 0.05). After inhibiting the expression of PRDX1, the protein expression level of PTEN and the protein ratio of p-AKT/AKT were significantly reduced, while the protein levels of SYN1 and BDNF were significantly increased (p < 0.05). This study, for the first time, demonstrates that PRDX1 affects ACR-induced neurotoxicity by regulating the PTEN/AKT signaling pathway. And, provides novel insights into the prevention and treatment of neurotoxicity in populations exposed to ACR.
{"title":"PRDX1 affects acrylamide-induced neural damage through the PTEN/AKT signaling pathway","authors":"Dong-Xue Fu , Ya-Ting Lei , Hai-Bo Guo , Ting Chen , Xiang-Ying Gao , Xiao-Li Wang , Xiang Huang , Ling-Ling Song , Sheng-Yuan Wang , Qin-Xue Dai","doi":"10.1016/j.neuro.2025.04.003","DOIUrl":"10.1016/j.neuro.2025.04.003","url":null,"abstract":"<div><div>Peroxiredoxin 1 (PRDX1) is a member of the peroxidase family of antioxidant enzymes. However, the role and mechanism of PRDX1 in acrylamide (ACR)-induced nerve damage have not been reported. We used SD rats and well-differentiated rat pheochromocytoma cells (PC-12 cells) to established <em>in vivo</em> and <em>in vitro</em> models of ACR. Immunohistochemistry, immunofluorescence and RT-qPCR experiments were used to detect the expression of PRDX1 in neurons of rat hippocampal tissue. The ultrastructural changes of neurons and PC-12 cells in rat hippocampal tissue were observed under transmission electron microscope. Western blot detected the protein expression levels of PRDX1, PTEN, AKT and p-AKT. <em>In vivo</em> and <em>in vitro</em> experimental results showed that PRDX1 showed a significant up-regulation trend after ACR exposure (<em>p</em> < 0.05). <em>In vitro</em> experiments showed that after inhibiting PRDX1 expression with PRDX1 siRNA, the survival rate of PC-12 cells significantly increased, and the damage to cell morphology and organelles was markedly improved. Western blot analysis revealed that ACR exposure can cause a significant increase in PTEN protein expression level and p-AKT/AKT protein ratio (<em>p</em> < 0.05). After inhibiting the expression of PRDX1, the protein expression level of PTEN and the protein ratio of p-AKT/AKT were significantly reduced, while the protein levels of SYN1 and BDNF were significantly increased (<em>p</em> < 0.05). This study, for the first time, demonstrates that PRDX1 affects ACR-induced neurotoxicity by regulating the PTEN/AKT signaling pathway. And, provides novel insights into the prevention and treatment of neurotoxicity in populations exposed to ACR.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 150-158"},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792337","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 : 2025-04-03DOI: 10.1016/j.neuro.2025.04.002
Luis Terrazas-Salgado , Miguel Betancourt-Lozano , Alejandra García-Gasca , Isabel Alvarado-Cruz
N-(phosphonomethyl)glycine (glyphosate) is the most widely used herbicide worldwide. Although it has been extensively studied, few studies use realistic environmental concentrations to assess its potential effects on fish embryos and larvae. This work aims to evaluate potential neurotoxic and reproductive effects of realistic concentrations of glyphosate in non-target aquatic species using zebrafish larvae. Biological and reproductive biomarkers (condition factor, hepatic and gonadic indices, and fertility rate) were evaluated for adults exposed to 0, 10, 100, and 1000 µg/L, while a transcriptomic comparison was carried out for larvae from both exposure scenarios at 1000 µg/L. The fertility rate of exposed parents decreased with increasing glyphosate concentration, while gonadosomatic (GSI) and hepatosomatic (HIS) indices of females treated with 100 µg/L glyphosate were significantly higher in glyphosate-exposed fish compared to the control group; however, glyphosate treatment did not significantly change GSI or HSI in males. Transcriptomic analysis in larvae showed that glyphosate could alter developmental and metabolic processes, targeting the nervous system in both exposure schemes. The ability of glyphosate to alter the development of the nervous system in larvae of exposed parents suggests that exposure to gametes could produce intergenerational alterations, with potential ecotoxicological implications that remain to be determined.
{"title":"Environmental concentrations of glyphosate through direct or parental exposure alter nervous system development and reduce the fertility rate in zebrafish","authors":"Luis Terrazas-Salgado , Miguel Betancourt-Lozano , Alejandra García-Gasca , Isabel Alvarado-Cruz","doi":"10.1016/j.neuro.2025.04.002","DOIUrl":"10.1016/j.neuro.2025.04.002","url":null,"abstract":"<div><div>N-(phosphonomethyl)glycine (glyphosate) is the most widely used herbicide worldwide. Although it has been extensively studied, few studies use realistic environmental concentrations to assess its potential effects on fish embryos and larvae. This work aims to evaluate potential neurotoxic and reproductive effects of realistic concentrations of glyphosate in non-target aquatic species using zebrafish larvae. Biological and reproductive biomarkers (condition factor, hepatic and gonadic indices, and fertility rate) were evaluated for adults exposed to 0, 10, 100, and 1000 µg/L, while a transcriptomic comparison was carried out for larvae from both exposure scenarios at 1000 µg/L. The fertility rate of exposed parents decreased with increasing glyphosate concentration, while gonadosomatic (GSI) and hepatosomatic (HIS) indices of females treated with 100 µg/L glyphosate were significantly higher in glyphosate-exposed fish compared to the control group; however, glyphosate treatment did not significantly change GSI or HSI in males. Transcriptomic analysis in larvae showed that glyphosate could alter developmental and metabolic processes, targeting the nervous system in both exposure schemes. The ability of glyphosate to alter the development of the nervous system in larvae of exposed parents suggests that exposure to gametes could produce intergenerational alterations, with potential ecotoxicological implications that remain to be determined.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 169-179"},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788316","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 : 2025-03-22DOI: 10.1016/j.neuro.2025.03.005
Thiago N. Gardin, Weeberb J. Requia
The impact of wildfire smoke exposure on public health has been extensively studied, yet its potential consequences on academic performance remain relatively unexplored, particularly in the context of fire-prone regions, such as Brazil. We conducted a nationwide study of more than 40 million high school students in Brazil who took the National High School Exam (ENEM) between 2000 and 2020. We used mixed-effects regression models with state-specific random intercepts to examine the associations between the wildfire events and academic performance among Brazilian students. We accounted for multiple covariates, including socioeconomic status, spatiotemporal factors, air pollutants, and weather variables. We also explored the effect modification by exam subject (general subjects and essay), school management (private and public schools), location (urban and rural schools), and time period. Our findings suggest that increased wildfire events are associated with lower academic performance in both essay and general subjects. After adjustments for the covariates, the primary analysis results indicate a negative impact of wildfires on essay writing, with an estimated coefficient of −0.09 (95 % CI: −0.13; −0.05) with 100 wildfire records increase. Similarly, an increase of 100 wildfire records per year corresponded to a decrease of 0.10 (95 % CI: 0.06; 0.11) points for general subjects. This effect on academic performance was associated with a reduction of 0.33 % (95 %CI: 0.31 %; 0.34 %) in essay and 0.54 % (95 %CI: 0.52 %; 0.56 %) in general subjects. Our findings highlight the need for further attention to the influence of wildfire smoke exposure on student academic performance, suggesting that even small associations at the individual level could have broader implications for public health and education policies.
{"title":"The effect of wildfire smoke exposure on student performance: A nationwide study across two decades (2000–2020) and over 40 million students in Brazil","authors":"Thiago N. Gardin, Weeberb J. Requia","doi":"10.1016/j.neuro.2025.03.005","DOIUrl":"10.1016/j.neuro.2025.03.005","url":null,"abstract":"<div><div>The impact of wildfire smoke exposure on public health has been extensively studied, yet its potential consequences on academic performance remain relatively unexplored, particularly in the context of fire-prone regions, such as Brazil. We conducted a nationwide study of more than 40 million high school students in Brazil who took the National High School Exam (ENEM) between 2000 and 2020. We used mixed-effects regression models with state-specific random intercepts to examine the associations between the wildfire events and academic performance among Brazilian students. We accounted for multiple covariates, including socioeconomic status, spatiotemporal factors, air pollutants, and weather variables. We also explored the effect modification by exam subject (general subjects and essay), school management (private and public schools), location (urban and rural schools), and time period. Our findings suggest that increased wildfire events are associated with lower academic performance in both essay and general subjects. After adjustments for the covariates, the primary analysis results indicate a negative impact of wildfires on essay writing, with an estimated coefficient of −0.09 (95 % CI: −0.13; −0.05) with 100 wildfire records increase. Similarly, an increase of 100 wildfire records per year corresponded to a decrease of 0.10 (95 % CI: 0.06; 0.11) points for general subjects. This effect on academic performance was associated with a reduction of 0.33 % (95 %CI: 0.31 %; 0.34 %) in essay and 0.54 % (95 %CI: 0.52 %; 0.56 %) in general subjects. Our findings highlight the need for further attention to the influence of wildfire smoke exposure on student academic performance, suggesting that even small associations at the individual level could have broader implications for public health and education policies.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 143-149"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692808","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 : 2025-03-20DOI: 10.1016/j.neuro.2025.03.008
Yue He, Yan Xu, Chengxiang Hu, Lina Jin
Phthalates have raised concerns on health outcomes including depression, due to its ubiquity. Knowledge is lacking on the role of modifiable lifestyle in attenuating phthalates’ adverse effects. We aimed to evaluate the interaction effects of lifestyle with urinary phthalate metabolites (UPMs) on depression. A total of 3588 participants aged ≥ 20 from the National Health and Nutrition Examination Survey 2011–2018 were involved. We used multivariate logistic regression models and Bayesian Kernel Machine Regression models to evaluate the associations of UPMs (individual or mixture) and lifestyle with depression. Positive associations of individual UPMs and its mixture with depression were observed in total population and participants maintaining an unfavorable lifestyle. No such association was found in participants with a healthy lifestyle. Interactions between lifestyle category with MECPP (P for interaction = 0.028), and ΣDEHP (P for interaction = 0.087) on depression were observed. Additionally, smoking, alcohol consumption and physical activity in healthy levels showed the greatest effect against depression among the common lifestyle combinations. In conclusion, positive associations of UPMs with depression risk, and interaction effects of lifestyle and UPMs on depression were observed. Our findings indicate that healthy lifestyle might weaken the adverse effects of phthalate exposure on depression risk.
{"title":"Does healthy lifestyle attenuate the associations of phthalates with depression? A cross-sectional study","authors":"Yue He, Yan Xu, Chengxiang Hu, Lina Jin","doi":"10.1016/j.neuro.2025.03.008","DOIUrl":"10.1016/j.neuro.2025.03.008","url":null,"abstract":"<div><div>Phthalates have raised concerns on health outcomes including depression, due to its ubiquity. Knowledge is lacking on the role of modifiable lifestyle in attenuating phthalates’ adverse effects. We aimed to evaluate the interaction effects of lifestyle with urinary phthalate metabolites (UPMs) on depression. A total of 3588 participants aged ≥ 20 from the National Health and Nutrition Examination Survey 2011–2018 were involved. We used multivariate logistic regression models and Bayesian Kernel Machine Regression models to evaluate the associations of UPMs (individual or mixture) and lifestyle with depression. Positive associations of individual UPMs and its mixture with depression were observed in total population and participants maintaining an unfavorable lifestyle. No such association was found in participants with a healthy lifestyle. Interactions between lifestyle category with MECPP (<em>P</em> for interaction = 0.028), and ΣDEHP (<em>P</em> for interaction = 0.087) on depression were observed. Additionally, smoking, alcohol consumption and physical activity in healthy levels showed the greatest effect against depression among the common lifestyle combinations. In conclusion, positive associations of UPMs with depression risk, and interaction effects of lifestyle and UPMs on depression were observed. Our findings indicate that healthy lifestyle might weaken the adverse effects of phthalate exposure on depression risk.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 134-142"},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685452","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号