Neurotoxicology最新文献

{"title":"Protective role of root-derived betulinic acid from Artocarpus heterophyllus against arsenic-induced neurotoxicity in Drosophila melanogaster","authors":"B. Srihari ,&nbsp;K.V. Harish Prashanth","doi":"10.1016/j.neuro.2025.06.002","DOIUrl":"10.1016/j.neuro.2025.06.002","url":null,"abstract":"<div><div>Exposure to arsenic (<strong>As</strong>) has several adverse health effects, including cognitive deficits in humans and animals. In the present study, neuroprotective effect of <em>Artocarpus heterophyllus</em> root derived purified (98 %) betulinic acid powder (BAP) was examined against <strong>As</strong> induced neurotoxicity in <em>Drosophila melanogaster</em> (Oregon K, wild type). BAP was well characterized using HPTLC and LC-MS. Adult flies treated with <strong>As</strong> alone showed significant behaviour deficits, enhanced oxidative stress, neurotoxicity, and mortality. Further, flies were co-fed with BAP along with <strong>As</strong> (0.5 mM) for 7 days. As a result, BAP decreased the mortality rate in a concentration dependent manner against <strong>As</strong> toxicity (36–77 %). Behavioural studies indicated that flies treated with BAP had an improved locomotor phenotype and increased survival potential (18 days) for <strong>As</strong> induced flies. The biochemical analysis revealed that BAP restored <strong>As</strong> induced elevation of oxidative markers in both head and body regions of flies. BAP enhanced the activity of membrane-bound enzymes such as succinate dehydrogenase and NADH-cytochrome c reductase. Additionally, it was found that BAP alleviated cholinergic disturbances and dopamine depletion, which are associated with <strong>As</strong> and bring down abnormal brain architecture to normal. Overall, data suggests that BAP may provide neuromodulatory effects against <strong>As</strong>-induced neurotoxicity by suppressing oxidative stress and attenuating mitochondrial dysfunction.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 80-91"},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of insufficient sleep on subjective cognitive dysfunction: Exploring the moderating role of environmental factors at the census tract level","authors":"Emily Feldman,&nbsp;Amanda Bates,&nbsp;Danica C. Slavish","doi":"10.1016/j.neuro.2025.06.001","DOIUrl":"10.1016/j.neuro.2025.06.001","url":null,"abstract":"<div><div>Subjective cognitive decline (SCD) affects approximately 50 % of adults in the United States. Insufficient sleep (&lt; 7 h per night) and environmental hazards (e.g., exposure to traffic, hazardous chemicals, and air pollution) have each been identified as independent risk factors for cognitive dysfunction. Furthermore, sleep duration and environmental hazards may interact to exacerbate cognitive dysfunction. However, this has yet to be tested empirically using nationally representative data. Using the CDC PLACES and EPA EJScreen datasets, we examined the associations between insufficient sleep, environmental hazards (particulate matter &lt; 2.5 micrometers [PM_2.5], Superfund site proximity, traffic volume/proximity), and cognitive dysfunction across 58,014 U.S. Census tracts. Multiple regression analyses revealed that insufficient sleep and more environmental hazard exposure (i.e., higher levels of PM_2.5, and higher volume/closer proximity to traffic) were each significantly associated with an increased prevalence of cognitive dysfunction. Significant interactions also were observed between insufficient sleep and environmental hazards: In Census tracts with higher exposure to PM_2.5, closer proximity/higher volume of traffic, and farther proximity from a Superfund site there was a stronger association between insufficient sleep and cognitive dysfunction. These findings underscore the importance of addressing multiple environmental and behavioral risk factors in efforts to mitigate cognitive dysfunction. The synergistic effects observed highlight the need for integrated interventions that target both sleep health and environmental exposures to improve cognitive health outcomes and promote health equity, especially in underserved populations.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 66-79"},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285797","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":"Occupational aluminum exposure in northern China’s large-scale plants: Unveiling dual-pathway mediation of fasting blood glucose and systolic blood pressure in cognitive impairment among workers","authors":"Xin Guo ,&nbsp;Qiang Yang ,&nbsp;Fangyu Gao ,&nbsp;Baolong Pan ,&nbsp;Feng Gao ,&nbsp;Jingsi Zhang ,&nbsp;Shanshan Wang ,&nbsp;Xiaoting Lu ,&nbsp;Jing Song ,&nbsp;Linping Wang ,&nbsp;Huifang Zhang ,&nbsp;Qiao Niu","doi":"10.1016/j.neuro.2025.05.011","DOIUrl":"10.1016/j.neuro.2025.05.011","url":null,"abstract":"<div><h3>Introduction</h3><div>The relationship between aluminium exposure and cognitive impairment remains to be fully elucidated. Furthermore, studies examining potential mediating mechanisms are limited. Objectives: The study investigated the relationship between plasma aluminium (P-Al) levels and cognitive impairment (was defined as a Montreal Cognitive Assessment (MoCA) score &lt; 26 (i.e., mild cognitive impairment, MCI). The parallel mediating effects of systolic blood pressure (SBP) and fasting blood glucose (FBG) in the association between plasma aluminum (P-Al) and cognitive function were analyzed.</div></div><div><h3>Methods</h3><div>In this cross-sectional study of 229 aluminum workers (2024 survey), we conducted a three-step analysis:Descriptive statistics: Demographic and clinical variables were summarized as mean ± SD or median (IQR) for continuous data, and frequencies (%) for categorical data.Group comparisons: ANOVA with Bonferroni correction (normal-distributed variables) and Kruskal-Wallis H test were used to compare differences across P-Al quartiles (Q_{1 -} Q₄). Categorical variables were analyzed by χ² or Fisher’s exact tests.Mediation analysis: A dual-pathway mediation model (SBP and FBG as parallel mediators) was tested using bootstrap method. Effects were reported as standardized β coefficients with 95 % CIs.</div></div><div><h3>Results</h3><div>Workers in the high P-Al group had significantly lower MoCA scores (<em>P</em> &lt; 0.05) and higher incidence of cognitive dysfunction (<em>P</em> &lt; 0.05). <em>P</em>-Al levels were negatively correlated with MoCA scores (r = -0.716, <em>P</em> &lt; 0.05) and indirectly affected cognitive function through the parallel mediating pathways of SBP (7.41 % of indirect effect) and FBG (18.52 % of indirect effect), with the direct effect accounting for 74.07 % of the total effect.</div></div><div><h3>Conclusion</h3><div>Aluminum exposure is significantly associated with cognitive impairment, which may have dual effects on metabolic disorders (elevated FBG) and vascular damage (elevated blood pressure) pathways.In order to reduce the risk of occupational cognitive dysfunction, it is necessary to implement enhanced P-Al monitoring and metabolic index interventions for aluminium workers.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 59-65"},"PeriodicalIF":3.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232605","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":"Environmental adversity, endoplasmic reticulum stress, and neurogenesis","authors":"Zuohui Zhang,&nbsp;Wen Wen,&nbsp;Di Hu,&nbsp;Hui Li,&nbsp;Hong Lin,&nbsp;Jia Luo","doi":"10.1016/j.neuro.2025.05.010","DOIUrl":"10.1016/j.neuro.2025.05.010","url":null,"abstract":"<div><div>Environmental adversity experienced during the prenatal period can include maternal nutritional deficiency, infectious agents, heavy metals, industrial chemicals, air pollution, medication, alcohol exposure, and substance use, as well as maternal factors such as diabetes. If these adversities occur during certain developmental time windows, they can significantly impact fetal development and have long-lasting neurobehavioral deficits. However, molecular mechanisms underlying the impact of environmental adversity remains unclear. The process by which new neurons form in the brain is neurogenesis. In certain brain regions neurogenesis continues throughout the lifespan and is essential for continued neurodevelopment and good mental health. Appropriate cellular responses to both extrinsic and intrinsic stressors require maintenance of the proteome, which relies on homeostasis of the endoplasmic reticulum (ER). Perturbations of ER homeostasis, such as the depletion of nutrients and disturbances in calcium or redox status, lead to abnormal accumulation of misfolded proteins and induce ER stress, which is monitored by the unfolded protein response (UPR). UPR is an adaptive reaction that restores protein homeostasis or triggers apoptotic cell death. Recent research indicates that ER stress during development can impair neurogenesis. We hypothesize that ER stress-mediated disruption of neurogenesis underlies the neurobehavioral deficits caused by environmental adversity. In this review, we discuss evidence of the impact that environmental adversities have on neurogenesis and the involvement of ER stress. We also discuss crosstalk across ER stress, oxidative stress, autophagy, and neuroinflammation, as well as potential therapeutic strategies that target ER stress/UPR for the treatment of neurobehavioral deficits associated with environmental adversities.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 32-45"},"PeriodicalIF":3.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195813","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 and gastroprotective effects of rutin and fluoxetine Co-supplementation: A biochemical analysis in Nauphoeta cinerea","authors":"Carlos Alonso Leite dos Santos ,&nbsp;Antonia Adeublena de Araújo Monteiro ,&nbsp;Mateus Santana de Deus ,&nbsp;Jean Paul Kamdem ,&nbsp;Antonia Eliene Duarte ,&nbsp;Mashal M. Almutairi ,&nbsp;Abid Ali ,&nbsp;Mohammad Ibrahim","doi":"10.1016/j.neuro.2025.05.009","DOIUrl":"10.1016/j.neuro.2025.05.009","url":null,"abstract":"<div><div>A significant portion of the global population is affected by depression, leading to considerable social and economic burdens. Although antidepressants such as fluoxetine are effective, their prolonged use is often associated with adverse side effects. This study investigated the biochemical effects of fluoxetine and rutin, individually and in combination, using the <em>Nauphoeta cinerea</em> model. Cockroaches were supplemented with the compounds for seven days, during which toxicity, body weight, and food intake were monitored. At the end of the treatment, neural and intestinal tissues were subjected to biochemical analyses, and <em>in silico</em> evaluations of the compounds were also performed. Co-supplementation with rutin (5 mg/mL) and fluoxetine (20 mg/mL) significantly reduced TBARS levels compared to fluoxetine alone and prevented the weight loss typically observed with fluoxetine treatment, despite similar food intake across groups. Rutin also mitigated the toxicity associated with fluoxetine administration. These findings suggest that rutin co-supplementation may attenuate fluoxetine-induced oxidative stress and toxicity, supporting its potential as a protective agent during antidepressant therapy.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 46-58"},"PeriodicalIF":3.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160703","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":"Inhibition of P2X7R by hypericin improves diabetic cardiac autonomic neuropathy through the proteasome- Nrf2 - GPX4 signaling axis","authors":"Yusen Sun ,&nbsp;Xiaoqian Ma ,&nbsp;Yanning Gong ,&nbsp;Hongmin Guo ,&nbsp;Congfa Zhou ,&nbsp;Qixing Hu ,&nbsp;Zhiying Zhou ,&nbsp;Yuanyuan Zhang ,&nbsp;Shangdong Liang ,&nbsp;Guilin Li","doi":"10.1016/j.neuro.2025.05.008","DOIUrl":"10.1016/j.neuro.2025.05.008","url":null,"abstract":"<div><div>Hypericin (HYP), a primary active compound derived from Hypericum perforatum has been studied in the context of diabetes. The purpose of this study is to observe whether HYP can improve diabetic cardiac autonomic neuropathy (DCAN) and its possible mechanism. The current findings suggest that multiple drivers of ferroptosis in DCAN converge on the antioxidant protein nuclear factor erythroid 2-related factor 2(Nrf2). Overactivated P2X7 receptor (P2X7R) increases Nrf2 degradation by increasing proteasome activity through calcium ion accumulation. This work showed that HYP inhibited P2X7R expression, leading to elevated Nrf2 levels, thereby counteracting ferroptosis. This inhibition improves abnormal changes in cardiac function during the pathological process of DCAN in diabetic rats, including heart rate (HR), blood pressure (BP), heart rate variability (HRV), and sympathetic nerve discharge (SND). In summary, HYP enhances Nrf2 protein levels by suppressing P2X7R expression, reducing calcium-induced proteasome activity, and inhibits ferroptosis and inflammation. Thus, HYP alleviated DCAN progression.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 1-10"},"PeriodicalIF":3.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139554","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":"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}