Neurotoxicology最新文献

{"title":"Fish consumption advice is depriving children of neurolipids and other nutrients essential to brain and eye development","authors":"Philip Spiller ,&nbsp;J. Thomas Brenna ,&nbsp;Susan E. Carlson ,&nbsp;Jean Golding ,&nbsp;Michael A. Crawford ,&nbsp;Joseph R. Hibbeln ,&nbsp;Berthold V. Koletzko ,&nbsp;John Columbo ,&nbsp;Penny Kris-Etherton ,&nbsp;Sonja L. Connor ,&nbsp;Clark Carrington ,&nbsp;P. Michael Bolger ,&nbsp;Joyce A. Nettleton ,&nbsp;William S. Harris ,&nbsp;Kristina Jackson ,&nbsp;Robert K. McNamara ,&nbsp;Kara M. Morgan ,&nbsp;Nicholas V.C. Ralston ,&nbsp;Laura Raymond ,&nbsp;Michael F. Tlusty ,&nbsp;Gary J. Myers","doi":"10.1016/j.neuro.2025.05.007","DOIUrl":"10.1016/j.neuro.2025.05.007","url":null,"abstract":"<div><div>A large and growing body of published research has found considerable evidence of improvements and little evidence of harm to children’s neurodevelopment, including IQ, when pregnant women eat more fish, particularly ocean species. Fish is the primary dietary source for people of omega-3 fatty acids that are essential building blocks for brain structure and function. The human body cannot synthesize adequate amounts of these omega-3s for optimal brain development so they must be obtained preformed, mainly from fish. However, the evidence indicates that women often reduce or eliminate their fish consumption when they become pregnant out of fear that methylmercury will harm their children’s neurodevelopment. This discrepancy between scientific findings and behavior appears to be caused or amplified by highly influential federal advice (fish advisories) that have been urging pregnant women to observe precautionary limitations on their consumption since 2001. Our concern is that these limitations are inadvertently encouraging pregnant women to avoid what could be substantial gains to their children’s neurodevelopment on a population-wide basis. We discuss how a new fish advisory based on the latest scientific findings could benefit children’s brain and cognitive development. We urge the academic/scientific community to develop and disseminate it and use it as a basis for education campaigns.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 27-31"},"PeriodicalIF":3.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127864","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 reference list of neurotoxicants based on CLP harmonised classifications","authors":"Kai Craenen,&nbsp;Panagiotis Kosiaras,&nbsp;Kati Hellsten","doi":"10.1016/j.neuro.2025.05.006","DOIUrl":"10.1016/j.neuro.2025.05.006","url":null,"abstract":"<div><div>With the societal interest to decrease experimental animal testing for regulatory purposes, the need for reliable new approach methods (NAMs) has become evident. To ensure the continued safe use of chemicals, NAMs should perform ideally at a comparable or better level of sensitivity and specificity as the in vivo modalities that they aim to replace, especially if they are to be used for hazard assessment. The use of relevant reference substances, selected with transparent criteria, forms a cornerstone of developing and validating (in silico and in vitro) NAMs. Claims on sensitivity and specificity should be based on results generated with reference chemicals that were previously scrutinised by independent expert panels on whether the substance has a hazardous property. CLP (Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures) forms a key pillar in EU chemicals management. The evaluation of all available information by the Committee for Risk Assessment (RAC) and their comparison to CLP classification criteria creates the opportunity to objectively compile lists of positive reference substances. We collated a reference list of neurotoxic substances to aid in the development of neurotoxicity NAMs. We screened CLP Annex VI and reflected on existing reference lists and mode of action data. The identified substances included industrial chemicals and active substances in plant protection products and biocidal products. This list of neurotoxicants is not an exhaustive consensus list, which ideally would be the result of combining this list with those generated by other authorities or expert groups.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 11-26"},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120367","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":"Neuroprotective effect of chicoric acid-loaded liposome nanoparticles against AlCl3-induced neurotoxicity in rats: Insights into the role of AMPK/AKT/Nrf-2 signaling pathway","authors":"Ahmed A. Sedik ,&nbsp;Soha A. Hassan ,&nbsp;Mahmoud A.E. Hassan ,&nbsp;Dalia O. Saleh","doi":"10.1016/j.neuro.2025.05.004","DOIUrl":"10.1016/j.neuro.2025.05.004","url":null,"abstract":"<div><div>Aluminum (Al) is the primary hazardous metal that individuals are exposed to in their daily lives via food, drinking water, and pharmaceuticals. The aim of this study was to evaluate the potential neuroprotective effect of chicoric acid-loaded liposome nanoparticles (CA nanoparticles) on aluminum chloride (AlCl3)-induced neurotoxicity in rats. CA nanoparticles were prepared using the thin-film hydration method, yielding nanoparticles with an average size of 146.3 nm, a polydispersity index (PDI) of 0.377, and a zeta potential of −41.8 mV, ensuring good stability. Thirty-two male Sprague-Dawley rats were allocated into four groups. The control group received saline, the control positive group was given AlCl3 (70 mg/kg/day p.o.) for 5 weeks, and the CA nanoparticle groups were given 2 doses (5 and 10 mg/kg/day p.o.) for 5 weeks, one hour after the injection of AlCl3. Behavioral tests, including open field and novel object tests, were conducted, and brain tissues were analysed for biochemical, molecular, histological and immune-histochemical changes at the end of the experiment. Compared with AlCl3, CA nanoparticles (10 mg/kg) improved the behavioral impairments and reduced the brain levels of acetylcholine esterase activity, glutamine, malondialdehyde, tumor necrosis factor-alpha, and interleukin-6 and increased the brain glutathione, nuclear factor erythroid 2-related factor 2 (Nrf-2), AKT signaling pathway, and AMP-activated kinase (AMPK) expression levels. Additionally, CA nanoparticles (10 mg/kg) improved histopathological changes and restored the immune-histochemical scores of glial fibrillary acidic proteins and the expression of Beclin. These findings revealed that CA nanoparticles (10 mg/kg) play a crucial role in the AMPK/AKT/Nrf-2 pathway, which is responsible for their antioxidant and anti-inflammatory effects against AlCl3-induced neurotoxicity in rats. These findings are paving the way for future investigations exploring the potential of CA nanoparticles in other neurodegenerative models, optimizing their formulation for enhanced brain targeting, and advancing their clinical translation as a therapeutic strategy.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 354-367"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946651","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":"Abnormal lipid metabolism and inflammatory response induced by aluminum led to the cognitive decline in mice","authors":"Rong Feng ,&nbsp;Zhongyao Chen ,&nbsp;Liang Chen ,&nbsp;Wei Wei ,&nbsp;Jiafeng Wen ,&nbsp;Jingyu Zheng","doi":"10.1016/j.neuro.2025.04.012","DOIUrl":"10.1016/j.neuro.2025.04.012","url":null,"abstract":"<div><div>As a chronic, low-toxicity metal, the effect of aluminum on human body has been paid more and more attention; however, the exact mechanism of action remains unclear. In this study, we studied the effects of aluminum on oxidative stress, inflammation, and mild cognitive impairment in mice, and analyzed changes in fecal metabolites to elucidate the potential mechanisms underlying these interactions. After 120 days of aluminum feeding, behavioral tests revealed that mice in the high-dose aluminum group exhibited cognitive decline. Regarding oxidative stress indices, MDA level increased, while GSH-PX activity, GSH content and CAT activity decreased significantly in aluminum treatment group. MAO activity increased and TC content decreased significantly. Pathological analysis of tissue sections showed that there was inflammation in brain tissue of high dose group. Pro-inflammatory factors TNF-α and IL-1β in brain tissue were significantly increased. Four metabolites (arachidic acid, linoleic acid squalene and <em>P</em>-cymene) involved in lipid metabolic pathways and inflammation varied significantly in the feces of each group. Therefore, aluminum-induced abnormal lipid metabolism pathway and inflammatory response may be an important cause of the cognitive decline.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 281-294"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892055","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":"Modification effect of healthy lifestyle among solid fuels and mild cognitive impairment in middle-aged and older adults: A prospective cohort study","authors":"Jie He ,&nbsp;Rui Yang ,&nbsp;Kangkang Zhong ,&nbsp;Chuanting Wen ,&nbsp;Xuechun Liu ,&nbsp;Yan Wang ,&nbsp;Qi Zhong","doi":"10.1016/j.neuro.2025.04.016","DOIUrl":"10.1016/j.neuro.2025.04.016","url":null,"abstract":"<div><div>To explore the association between solid fuels and mild cognitive impairment (MCI) and the role of the healthy lifestyle score (HLS) in the association between solid fuels and MCI. Data were obtained from CHARLS from 2011 to 2020. A logistic regression model which assessed the impact of solid fuel use on MCI was applied. A full HLS was constructed to evaluate the interaction and joint effects of HLS with solid fuels. 11054 people were enclosed in this study and the proportion of the population using solid fuels is as high as 74.05 % for heating fuels and 56.53 % for cooking fuels. Results showed that solid fuel use was positively associated with the risk of MCI during cooking and heating, with 95 % confidence intervals (95 % CI) of 1.11 (1.00, 1.23) for cooking and 1.14 (1.00, 1.31) for heating. Further, a healthy BMI was beneficial in reducing the harmful effects of solid fuels. Solid fuel use was significantly associated with MCI among middle-aged and older Chinese adults. Our results also suggested that higher HLS is beneficial in reducing the risk of MCI from solid fuels. In this study, we are prompted to use cleaner fuels and ventilation equipment along with the need to develop effective HLS measures for interventions.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 338-343"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937225","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":"2,4,6-trinitrotoluene induces neurotoxicity by affecting the G protein pathways in Caenorhabditis elegans","authors":"Ying Li ,&nbsp;Yanping Zhou ,&nbsp;Chunyan Wang ,&nbsp;Yaguang Nie ,&nbsp;Yongbing Zhu ,&nbsp;Sanping Zhao ,&nbsp;Lijun Wu ,&nbsp;An Xu","doi":"10.1016/j.neuro.2025.04.014","DOIUrl":"10.1016/j.neuro.2025.04.014","url":null,"abstract":"<div><div>2,4,6-trinitrotoluene (TNT) is a chemical widely used to make explosives, and its use of residues can lead to potential threats to both ecosystems and human health. A thorough understanding of the various toxic effects of TNT is essential for developing effective environmental protection and health safety measures. Thus, we employed <em>Caenorhabditis elegans</em> (<em>C. elegans</em>), a typical model organism, to explore the neurotoxic effects of TNT and the signaling pathways involved. The results showed that neurotoxicity induced by 10–100 ng/mL TNT was manifested in reduced behavioral capacity (head thrashes, body bends, and pharyngeal pumping rates), and inhibition of foraging behavior and ethanol avoidance behavior. Using fluorescence-labeled transgenic nematodes, it was found that TNT damaged dopaminergic and cholinergic neurons, which resulted in a significant decrease in the release of neurotransmitters and the expression of associated genes (<em>dat-1</em> and <em>unc-17</em>). We studied the role of G protein signaling pathways and discovered that the related genes (<em>egl-30</em>, <em>gsa-1</em>, <em>goa-1</em>, and <em>unc-13</em>) were significantly down-regulated, resulting in reduced acetylcholine release, which in turn corresponded to the observed behavioral abnormality and damaged neurons in the worms. This study shed light on TNT’s neurotoxic mechanisms and associated health risks.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 328-337"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922232","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":"Neuroprotective effect of Licochalcone A against aluminum chloride-induced neurotoxicity by reducing Aβ accumulation, oxidative stress and inflammatory reaction","authors":"Zhijuan Tang ,&nbsp;Fang Wang ,&nbsp;Jintao Lv ,&nbsp;Gaohong Yang ,&nbsp;Xinchun Shen ,&nbsp;Fei Zeng ,&nbsp;Lingling Meng ,&nbsp;Wen Zhou ,&nbsp;Libin Zhan ,&nbsp;Zebin Weng","doi":"10.1016/j.neuro.2025.04.011","DOIUrl":"10.1016/j.neuro.2025.04.011","url":null,"abstract":"<div><div>Excessive aluminum exposure is a contributing factor in several neurodegenerative diseases. Natural plant compounds such as Licochalcone A have been shown to have significant neuroprotective effects <em>in vivo</em> and <em>in vitro</em>. In this study, we aim to elucidate the neuroprotective effect of Licochalcone A against aluminum chloride-induced neurotoxicity and its possible mechanism. Adult zebrafish and PC12 cells were used as animal and cell models. Zebrafish and PC12 cells were treated with excessive aluminum trichloride (100 μg/L aluminum chloride hexahydrate solutions for zebrafish or 500 μM Al-malt solution for PC12 cells) to cause neuronal damage. The neuroprotective effect of Licochalcone A was evaluated by measuring ROS production, Aβ_1–42 accumulation, inflammatory cytokines, neuronal apoptosis-associated genes, and MAPK pathway-related proteins to elucidate the mechanism of Licochalcone A against aluminum chloride-induced neurotoxicity. Licochalcone A effectively reduced the level of ROS production and inflammatory cytokines in both zebrafish and PC12 cells treated with excessive aluminum trichloride. In addition, Licochalcone A reduced the expression of BACE1 and generation of Aβ_1–42 as well as the expression of p-JNK and MAPK, the key factor of the MAPK pathway. These results indicated that Licochalcone A has a remarkable neuroprotective effect against neurotoxicity induced by aluminum and has a high potential in the development of therapeutic drugs for neurodegenerative diseases.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 295-305"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892056","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":"Cumulative risk assessment as the pathway to public health protection for behavioral neurotoxicity","authors":"Deborah A. Cory-Slechta ,&nbsp;Cynthia J. Downs ,&nbsp;Marissa Sobolewski","doi":"10.1016/j.neuro.2025.04.015","DOIUrl":"10.1016/j.neuro.2025.04.015","url":null,"abstract":"<div><div>The formulation of adverse outcome pathways (AOPs) based on high-throughput <em>in vitro</em> new approach methods linking biochemical/mechanistic data with an apical endpoint considered an adverse outcome (AO), is increasingly proposed to accelerate the process of risk assessment for environmental chemical exposures. While a laudable goal, this approach ignores the extensive evidence demonstrating context-dependence of neurotoxicological consequences, including behavioral toxicity of chemical exposures. Such contextual modifiers can include environmental conditions (poverty, psychosocial stress, behavioral experience/history), physiological conditions (sex, period of exposure, nutritional status, brain region, exposure parameters), and genetic background. Context dependence represents a serious omission for AOP formulation because an environmental context can alter a chemical’s molecular targets, or potentially enhance toxicity through interactions with other contextual conditions, thus leading to potential underestimation of neurological risks due to such exposures. The integrative physiological basis of AOs requires cumulative risk assessments that model environmental contexts across scales of biology, i.e., integration and testing in whole-animal models. AOPs contribute to the derivation of cumulative risk considerations regarding factors to incorporate into cumulative risk assessments by defining risk factors with shared biological targets. Epidemiological and animal model studies can provide information to prioritize interactive effects of greatest magnitude. Additionally, a focus on how a single risk factor in different physiological contexts may attribute risk across multiple neurologic conditions, rather than to a single unique condition, would provide broader public health protection. Realistic acknowledgement of context-dependence is requisite to understanding both the etiological basis of neurological diseases and disorders and to human health protection.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 400-411"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972370","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":"Developmental neurotoxicity of bisphenol F and bisphenol S in animal model systems: A literature review","authors":"Ricardo Cantua,&nbsp;Kimberly Mulligan","doi":"10.1016/j.neuro.2025.04.008","DOIUrl":"10.1016/j.neuro.2025.04.008","url":null,"abstract":"<div><div>Neurodevelopmental disorders have complex etiologies, stemming both from genetic and environmental risk factors, including gestational exposure to bisphenol A (BPA). BPA is an endocrine-disrupting chemical widely used in the synthesis of plastics and epoxy-resins. In 2012, the Food and Drug Administration issued a ban on the use of BPA in certain baby and childhood products, which contributed to the proliferation of BPA-free products. To make products without BPA, plastic and epoxy manufacturers often use chemical analogs, including bisphenol F (BPF) and bisphenol S (BPS). However, the structural and biochemical similarities BPF and BPS share with BPA suggest they may have similar molecular and cellular impacts on the developing nervous system, despite consumers generally regarding BPA-free products as safer alternatives. In this review, we synthesized all available peer-reviewed primary literature to date reporting on the neurodevelopmental impacts of BPF and/or BPS in animal models. In total, 61 papers were identified as relevant to the topic, including evaluation of BPF- and BPS-associated neurodevelopmental phenotypes such as changes in neurodevelopmental gene expression, the proliferation and differentiation of neural stem cells, synaptogenesis, central nervous system morphology, neuronal cell death, and behavior. Though less extensively studied than BPA, the collective works described here indicate that BPF and BPS can act as developmental neurotoxicants in animal models, urging further mechanistic and epidemiological analyses of these bisphenol analogs, as well as a reconsideration by regulatory agencies of policies surrounding their usage.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 263-280"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892057","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":"Multi-behavioral fingerprints can identify potential modes of action for neuroactive environmental chemicals","authors":"Nadia K. Herold ,&nbsp;Sebastian Gutsfeld ,&nbsp;David Leuthold ,&nbsp;Chloe Wray ,&nbsp;Julia Spath ,&nbsp;Tamara Tal","doi":"10.1016/j.neuro.2025.05.001","DOIUrl":"10.1016/j.neuro.2025.05.001","url":null,"abstract":"<div><div>There is a lack of confidence in the relevance of zebrafish-based behavior data for chemical risk assessment. We extended an automated Visual and Acoustic Motor Response (VAMR) new approach method (NAM) in 5-day post-fertilization (dpf) zebrafish to include 26, behavior-based endpoints that measure visual-motor responses, visual and acoustic startle responses, habituation learning, and memory retention. A correlation analysis from 5159 control larvae revealed that more complex endpoints for learning- and memory-related behavior yielded unique behavior patterns. To build confidence in the VAMR NAM, we established neuroactivity fingerprints using concentration-response profiles derived from 63 reference chemicals targeting neurotransmission, neurodevelopmental signaling, or toxicologically-relevant pathways. Hierarchical clustering revealed diverse toxicity fingerprints. Compounds that targeted the N-Methyl-D-aspartic acid (NMDA) or gamma-aminobutyric acid type A (GABA_A) receptors reduced habituation learning. Pathway modulators targeting peroxisome proliferator-activated receptor delta (PPARδ) or gamma (PPARγ), GABA_A, dopamine, ryanodine, aryl hydrocarbon (AhR), or G-protein-coupled receptors or the tyrosine kinase SRC inappropriately accelerated habituation learning. Reference chemicals targeting GABA_A, NMDA, dopamine, PPARα, PPARδ, epidermal growth factor, bone morphogenetic protein, AhR, retinoid X, or α2-adreno receptors triggered inappropriate hyperactivity. Exposure to GABA_A receptor antagonists elicited paradoxical excitation characterized by dark-phase sedation and increased startle responses while exposure to GABA_A/B receptor agonists altered the same endpoints with opposite directionality. Relative to reference chemicals, environmental chemicals known to be GABA receptor antagonists (Lindane, Dieldrine) or agonists (Tetrabromobisphenol A (TBBPA)) elicited predicted behavior fingerprints. When paired with the phenotypically rich VAMR NAM, behavior fingerprints are a powerful approach to identify neuroactive chemicals.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 377-399"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003025","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}