Neurotoxicology最新文献

{"title":"1-Octen-3-ol exacerbates depression-induced neurotoxicity via the TLR4/NF-κB and Nrf2/HO-1 pathways","authors":"Hao Song ,&nbsp;Yongjiao Wang ,&nbsp;Liyuan Ren ,&nbsp;Anxiang Su ,&nbsp;Minhao Xie ,&nbsp;Hui Xu ,&nbsp;Jianhui Liu ,&nbsp;Yizhou Liu ,&nbsp;Wenjian Yang","doi":"10.1016/j.neuro.2025.03.002","DOIUrl":"10.1016/j.neuro.2025.03.002","url":null,"abstract":"<div><div>1-Octen-3-ol is a volatile compound widely found in various fungi and plants, and studies have suggested its potential role in the development of neurodegenerative diseases. However, the mechanism by which 1-octen-3-ol induces neural injury in rats remains unclear. In this study, we used aerosolized 1-octen-3-ol to treat depressive model rats to investigate its effects on neural injury behaviors and neurophysiology in SD rats. The results showed that 1-octen-3-ol significantly increased the lung index to 0.47, reduced the sucrose preference rate to 42.9 %, decreased spontaneous exploration in the open field test, and increased immobility time in the forced swim test. Furthermore, 1-octen-3-ol disrupted blood-brain barrier permeability by reducing the expression of tight junction proteins Occludin and Claudin-1. It also promoted corticosterone secretion, reduced the release of monoamines (serotonin and norepinephrine) and amino acid neurotransmitters (5-hydroxytryptophan), and increased pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), leading to neuroendocrine damage. Additionally, it reduced the expression of synaptic proteins (PSD-95, Synapsin, and NMDA1) and neurotrophic factors (NT3 and NT4), resulting in impaired neuroplasticity. Simultaneously, 1-octen-3-ol activated the TLR4/NF-κB inflammatory pathway and suppressed the expression of the Nrf2/HO-1 antioxidant pathway, exacerbating neural injury in rats. These findings provide a mechanistic basis for the exacerbation of depression-induced neural injury by 1-octen-3-ol.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 81-93"},"PeriodicalIF":3.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610618","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":"Role of dopaminergic RE1-silencing transcription factor (REST) in manganese-induced behavioral deficits and dysregulating dopaminergic and serotonergic neurotransmission in mice","authors":"Sanghoon Kim ,&nbsp;Edward Pajarillo ,&nbsp;Alexis Digman ,&nbsp;Itunu Ajayi ,&nbsp;Deok-Soo Son ,&nbsp;Michael Aschner ,&nbsp;Eunsook Lee","doi":"10.1016/j.neuro.2025.03.001","DOIUrl":"10.1016/j.neuro.2025.03.001","url":null,"abstract":"<div><div>Chronic exposure to elevated levels of manganese (Mn) induces manganism, a neurological disorder, exhibiting symptoms resembling Parkinson’s disease (PD). Mn is well known to dysregulate dopaminergic (DAergic) function, while the repressor element-1 silencing transcription factor (REST) induces protection against Mn-induced toxicity and several neurodegenerative diseases, including PD and Alzheimer’s disease. In the present study, we investigated if DAergic REST plays a role in Mn-induced neurotoxicity by assessing behavioral deficits and alteration of neurotransmitter levels using high-performance liquid chromatography with electrochemical detector (HPLC-ECD), and microdialysis between DAergic-specific REST-deleted (REST cKO) mice and REST loxP mice as wild-type (WT) controls. Mice were exposed to Mn (330 μg, daily intranasal instillation for 3 weeks), followed by assessment of locomotor activity and novel object recognition, and subsequent brain dissection. Neurotransmitters, including DA, serotonin (5-HT), norepinephrine (NE), and glutamate, were analyzed in different brain regions, such as the striatum, midbrain, cortex, hippocampus, and cerebellum. After Mn exposure, extracellular DA levels in the striatum were measured by HPLC-microdialysis. The results showed that DAergic REST deletion exacerbated Mn-induced behavioral deficits and decreased DA levels in the nigrostriatal regions of WT mice. REST cKO increased DA turnover rates (DOPAC/DA and HVA/DA) by 10-fold in the nigrostriatal regions, showing lesser effects in other brain regions. Mn decreased extracellular DA levels, as measured by microdialysis, in the striatum in both genotypes. Mn decreased cortical NE levels in both genotypes and further exacerbated in REST cKO, while Mn decreased nigrostriatal NE levels only in REST cKO mice. REST cKO reduced 5-HT levels in all brain regions tested compared to WT mice. Mn increased glutamate and GABA levels in the striatum and midbrain, while these Mn effects were not altered by REST cKO. Taken together, our findings demonstrate that DAergic REST deficiency exacerbates Mn-induced motor and cognitive deficits along with dysregulation of neurotransmitters, mainly DA, 5-HT, and NE, suggesting that DAergic REST is important in Mn-induced dysregulation of monoaminergic neurotransmission.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 57-68"},"PeriodicalIF":3.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586425","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 see-saw effect of neuroactive steroids and endocrine disrupting compounds on maternal mental health status","authors":"S. Aishwarya ,&nbsp;V.M. Vinodhini ,&nbsp;P. Renuka ,&nbsp;M. Anuradha ,&nbsp;R. Arul Saravanan","doi":"10.1016/j.neuro.2025.02.007","DOIUrl":"10.1016/j.neuro.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Antepartum depression, a non-psychotic mood disturbance occurring during pregnancy, is influenced by hormonal fluctuations and environmental endocrine disruptors. Despite its association with adverse postpartum outcomes, it has been studied to a limited extent. Hence, this study aims to investigate the association of neuroactive steroids, endocrine-disrupting compounds, and nutritional status of pregnant women with the manifestations of antepartum depressive symptoms.</div></div><div><h3>Materials and methods</h3><div>This cross-sectional study assessed 400 pregnant women in their third trimester for depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) and evaluated for severity using the Beck Depression Inventory-II. The concentrations of allopregnanolone, DHEA-S, bisphenol A, methyl paraben, estradiol, progesterone, oxytocin, vitamin B₁₂, folic acid, vitamin D, iron, magnesium and zinc were analysed. Statistical analysis included Mann Whitney U test, Chi-square test, Spearman Correlation, and Logistic regression.</div></div><div><h3>Results</h3><div>The prevalence of antepartum depressive symptoms was 23 %. Allopregnanolone, DHEA-S, bisphenol A, methyl paraben, estradiol, oxytocin, and TSH levels were associated with depressive symptoms. Reduced levels of allopregnanolone, DHEA-S, and estradiol, along with elevated bisphenol A levels, were identified as significant independent risk factors for antepartum depressive symptoms. Selective micronutrient deficiency was also noted. Risk cutoff for antepartum depressive symptoms was established for allopregnanolone (≤17.9 ng/ml), DHEA-S (≤0.20 µg/ml), bisphenol A (≥2027.1 pg/ml), and methyl paraben (≥1.15 µg/ml).</div></div><div><h3>Conclusion</h3><div>Our study on 400 antepartum women showed a 23 % prevalence of depressive symptoms, with significant association reported with reduced neuroactive steroids, elevated endocrine disruptors, lower reproductive hormones, and micronutrient deficiency. These findings emphasize the need for comprehensive screening, monitored nutritional supplementation, and hormonal assessments in effectively managing pregnancy-related depressive symptoms.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 48-56"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551859","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 prospective study of a whole blood metal mixture and depressive symptoms among Black women from Detroit, Michigan","authors":"Samantha Schildroth ,&nbsp;Birgit Claus Henn ,&nbsp;Ruth J. Geller ,&nbsp;Amelia K. Wesselink ,&nbsp;Kristen Upson ,&nbsp;Anissa I. Vines ,&nbsp;Marco Vinceti ,&nbsp;Quaker E. Harmon ,&nbsp;Donna D. Baird ,&nbsp;Ganesa Wegienka ,&nbsp;Lauren A. Wise","doi":"10.1016/j.neuro.2025.02.005","DOIUrl":"10.1016/j.neuro.2025.02.005","url":null,"abstract":"<div><div>Exposure to metals has been previously associated with depressive symptoms, but few studies have considered potential effects of metal mixtures. In addition, few previous studies have been conducted among Black women, who are disproportionately at risk for exposure to some metals and greater depression incidence and severity. We analyzed data from the Study of Environment, Lifestyle, and Fibroids (SELF), a prospective cohort study of reproductive-aged Black women from Detroit, to examine associations between a mixture of metals, metalloids, and trace elements (“metals”) and depressive symptoms (n = 1450). SELF participants self-identified as Black or African American and were 23–34 years of age at enrollment. We collected covariate information on structured questionnaires and whole blood samples at baseline. We quantified 17 metals in whole blood using inductively coupled plasma mass spectrometer triple quadruple or Direct Mercury Analyzer-80. Participants reported depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D) at the 20-month follow-up visit, where higher CES-D scores reflected greater depressive symptoms. We used quantile-based g-computation to estimate the cumulative association of the metal mixture with CES-D scores, adjusting for age, household income, educational attainment, body mass index, smoking status, alcohol intake, and parity. We estimated beta coefficients (with 95 % confidence intervals [CI]) as the percent difference in CES-D scores per quartile increase in all metals. A one-quartile increase in the metal mixture was associated with 14.8 % lower (95 % CI=-26.7 %, −1.1 %) CES-D scores, reflecting lower depressive symptoms. The mixture association was driven by nickel, copper, cesium, molybdenum, and lead. Other neurotoxic metals (cadmium, arsenic, mercury, chromium) were associated with greater depressive symptoms. Findings from this study suggest that exposure to a mixture of metals may affect depressive symptoms in Black women, with individual metals acting in opposing directions.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 94-104"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541539","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":"Hippocampal apoptosis: Molecular mechanisms triggered by toxic cannabinoid exposure: A narrative review","authors":"Habibeh Mashayekhi-sardoo ,&nbsp;Mahdiyeh Hedayati-Moghadam ,&nbsp;Yousef Baghcheghi","doi":"10.1016/j.neuro.2025.02.006","DOIUrl":"10.1016/j.neuro.2025.02.006","url":null,"abstract":"<div><div>Hippocampal apoptosis is increasingly recognized as a significant consequence of toxic cannabinoid exposure, with profound implications for cognitive function and mental health. This narrative review comprehensively examines the molecular mechanisms underlying cannabinoid-induced apoptosis, focusing on the interplay of various bioactive compounds and their effects on neuronal integrity. We begin by discussing the key players in cannabinoid biology, followed by a synthesis of findings from animal and clinical studies that highlight the neurotoxic potential of cannabinoids. Central to our analysis are the roles of neuroinflammation and oxidative stress, which exacerbate neuronal damage and contribute to cell death. The activation of cannabinoid receptors, particularly CB1 and CB2, is scrutinized for its dual role in mediating neuroprotective and neurotoxic effects. We explore calcium dysregulation as a critical mechanism that leads to excitotoxicity, mitochondrial dysfunction, and the activation of pro-apoptotic pathways. Additionally, we address the inhibition of anti-apoptotic proteins, induction of endoplasmic reticulum (ER) stress, and disruption of neurotransmitter systems, all of which further facilitate apoptosis in hippocampal neurons. Alterations in neurotrophic factor levels are also examined, as they play a vital role in neuronal survival and plasticity. Ultimately, this review underscores the multifaceted nature of cannabinoid-induced hippocampal apoptosis and calls for further research to elucidate these complex interactions, aiming to inform clinical practices and public health policies regarding cannabinoid use. The findings presented herein highlight the urgent need for a nuanced understanding of the risks associated with cannabinoid exposure, particularly in vulnerable populations.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 28-47"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534865","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":"Tanshinone IIA mitigates postoperative cognitive dysfunction in aged rats by inhibiting hippocampal inflammation and ferroptosis: Role of Nrf2/SLC7A11/GPX4 axis activation","authors":"Yan Yang ,&nbsp;Bo Wang ,&nbsp;Yichen Jiang ,&nbsp;Wan Fu","doi":"10.1016/j.neuro.2025.02.003","DOIUrl":"10.1016/j.neuro.2025.02.003","url":null,"abstract":"<div><h3>Objective</h3><div>Postoperative cognitive dysfunction (POCD) is a common and debilitating complication in elderly patients following surgery, leading to increased morbidity and reduced quality of life. This study aims to investigate the neuroprotective effects of Tanshinone IIA, a lipophilic compound derived from <em>Salvia miltiorrhiza</em>, in an aged rat model of POCD, and explore its underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>POCD model was established by a modified abdominal exploratory laparotomy. Rats were then intraperitoneally administered with Tanshinone IIA (10 mg/kg, 20 mg/kg, or 40 mg/kg) for 30 days. Cognitive functions were assessed using the morris water maze, novel object recognition test, and Y-maze test. Synaptic structures in the hippocampal CA1 region were examined by electron microscopy. Inflammatory and ferroptosis pathways were evaluated by measuring inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-4), nitric oxide synthase (iNOS) activity, lipid peroxidation products (malondialdehyde [MDA]; 4-hydroxy-2-nonenal [4-HNE]), Fe^2 + levels, and antioxidant enzymes (superoxide dismutase [SOD], glutathione [GSH]) using ELISA and commercial kits. mRNA and proteins levels were quantified by real-time quantitative polymerase chain reaction and western blot analysis.</div></div><div><h3>Results</h3><div>Tanshinone IIA significantly ameliorated cognitive deficits in aged POCD rats according to behavioral tests. It also restored synaptic ultrastructure in the hippocampal CA1 region and upregulated the expressions of synaptic proteins, including synapsin-1 and PSD-95. In addition, Tanshinone IIA effectively suppressed the hippocampal inflammatory pathway, as evidenced by the decreased levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), an increased level of the anti-inflammatory cytokine IL-4, and the upregulation of the iNOS/NO pathway in the hippocampus. Furthermore, Tanshinone IIA mitigated ferroptosis by reducing MDA and 4-HNE contents, lowering Fe²⁺ level, and enhancing SOD activity and GSH level. Notably, Tanshinone IIA activated the Nrf2/SLC7A11/GPX4 axis in the hippocampus of aged POCD rats.</div></div><div><h3>Conclusion</h3><div>These findings suggest that Tanshinone IIA exerts neuroprotective effects in an aged rat model of POCD by attenuating hippocampal inflammation and ferroptosis, primarily through the activation of the Nrf2/SLC7A11/GPX4 axis.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"107 ","pages":"Pages 62-73"},"PeriodicalIF":3.4,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437409","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":"World Trade Center response activities and cognitive health: A moderated mediation study of the role of surgical/nuisance dust mask usage","authors":"Yuan Yang ,&nbsp;Jaymie Meliker ,&nbsp;Lauren L. Richmond ,&nbsp;Frank D. Mann ,&nbsp;Minos Kritikos ,&nbsp;Dylan M. Smith ,&nbsp;Tesleem Babalola ,&nbsp;Melissa A. Carr ,&nbsp;Benjamin J. Luft ,&nbsp;Sean A.P. Clouston","doi":"10.1016/j.neuro.2025.02.002","DOIUrl":"10.1016/j.neuro.2025.02.002","url":null,"abstract":"<div><h3>Objective</h3><div>This study explores the relationship between World Trade Center (WTC) response activities (WRAs) and cognitive impairment (CI) and uses a moderated-mediation model to examine the role of wearing a surgical/nuisance dust mask.</div></div><div><h3>Methods</h3><div>This study includes 3285 WTC responders. Responders were placed into eight WRA groups based on self-report structured responses and free-text descriptions of activities at the WTC. The presence/absence of surgical/nuisance dust mask usage was self-reported. The outcome was CI as determined using a Montreal Cognitive Assessment score &lt; 23. Robust Poisson regression was used to examine the main effect, and counterfactual moderated-mediation analysis was used to determine the role of mask usage.</div></div><div><h3>Results</h3><div>The risk of CI was higher across most WRAs when compared to supervision. Mask usage was reported by 63 % of responders and varied across WRAs and was associated with a reduced risk of CI (adjusted risk ratio [aRR]=0.77, p = 0.008) after controlling for WRAs. Moderation effects indicated that responders are more likely to wear masks when encountering more dangerous exposures, even within the same WRA group. Responders in the WRA-enclosed group had a lower risk of CI through a moderated intermediary effect of mask usage (aRR=0.92, p = 0.05).</div></div><div><h3>Conclusion</h3><div>Surgical/nuisance dust mask usage provided mild protection against air pollution exposures during WTC response activities when compared to not wearing a mask. Results suggest that response workers at disaster sites might benefit from wearing surgical/nuisance dust masks when respirators are unavailable even when the air seems safe.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 1-10"},"PeriodicalIF":3.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441550","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":"Polysaccharide alleviates neurodegeneration and behavioral deficit by enhancing mitochondrial autophagy in chronic methamphetamine mice","authors":"Han Yang ,&nbsp;Yuanhe Wang ,&nbsp;Shan Liu ,&nbsp;Shan Zhang ,&nbsp;Yuemeng Chen ,&nbsp;Jiuyang Ding ,&nbsp;Shunqin Chen ,&nbsp;Faze Zhu ,&nbsp;Bing Xia ,&nbsp;Peng Luo ,&nbsp;Yubo Liu","doi":"10.1016/j.neuro.2025.02.004","DOIUrl":"10.1016/j.neuro.2025.02.004","url":null,"abstract":"<div><div>Methamphetamine (METH) is a psychostimulant drug widely abused because of its addictive properties.Its impact on the central nervous system is a major area of interest due to its unique ability to cross the blood-brain barrier, facilitated by its dual water and lipid solubility. Studies have indicated that oxidative stress, neuroinflammation, neuronal apoptosis, and mitochondrial dysfunction are primary mechanisms of METH-induced neurotoxicity. Mitophagy, a process regulated by the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) induced kinase 1 (PINK1)/Parkin signaling pathway, has emerged as a critical mechanism for preserving mitochondrial function. Polysaccharides derived from bamboo fungus have shown potential in mitigating neurotoxicity. However, the role of these polysaccharides in ameliorating methamphetamine-induced neurotoxicity remains unclear. This study aimed to investigate whether polysaccharides could alleviate neurodegeneration in a chronic METH mice model and elucidate the underlying mechanisms and elucidate the mechanisms underlying METH-induced neuronal damage.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"107 ","pages":"Pages 53-61"},"PeriodicalIF":3.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425799","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":"Silver nanoparticle (AgNP), neurotoxicity, and putative adverse outcome pathway (AOP): A review","authors":"Julie Juyoung Park ,&nbsp;Elaine M. Faustman","doi":"10.1016/j.neuro.2025.02.001","DOIUrl":"10.1016/j.neuro.2025.02.001","url":null,"abstract":"<div><div>Various silver nanoparticles (AgNPs) exist with different sizes, coatings, and shapes. AgNPs have unique physical and chemical properties, such as high surface-to-volume ratio and antimicrobial properties, which allow them to be used in a wide array of applications in consumer products and medical applications, including clothing, cosmetics, food packaging, medical devices, and wound dressings. They are also one of the most studied engineered nanomaterials (ENMs). Though the liver and lung have been identified as the primary targets of AgNP exposures, an increasing number of studies have reported accumulations of AgNPs in the brains of AgNP-exposed animals. These findings have raised concerns because the brain plays a critical function in our body and may have difficulty clearing AgNPs, unlike the liver and lung. Studies have been conducted to investigate potential neurotoxicity effects of AgNP exposures, but they use various types of AgNPs and routes of administration, which makes it difficult to compare across studies. Therefore, the goal of this review was to (1) assess factors that may affect AgNP-induced neurotoxicity, (2) identify potential mechanisms of neurotoxicity exerted by AgNPs, (3) review existing <em>in vitro</em> dose-response and <em>in vivo</em> exposure-response AgNP-induced neurotoxicity studies, and (4) provide an example application of benchmark doses (BMDs) in comparing across different studies. A combination of aggregate exposure pathway (AEP) and adverse outcome pathway (AOP) framework was utilized to link AgNP exposure sources and routes to molecular initiating events (MIEs) and then to adverse neurotoxicity outcomes at the cellular, organ, organism, and population levels. This review is the first to propose an AEP/AOP specific to AgNP-induced neurotoxicity, which may contribute toward identifying plausible key event relationships between MIEs and adverse neurotoxicity outcomes and improving the current risk assessment of AgNPs.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 11-27"},"PeriodicalIF":3.4,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389966","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":"Therapeutic potential of pranlukast against cuprizone-induced inflammatory demyelination and sensory impairment in mice: Comparison with fingolimod","authors":"Greice Nascimento Pires ,&nbsp;Renata Pereira Laurindo ,&nbsp;Luiza Dos Santos Heringer ,&nbsp;Stefanny Calixto da Silva ,&nbsp;Débora Magalhães Portela ,&nbsp;Ricardo Cardoso ,&nbsp;Ana Carolina de Pádua ,&nbsp;Ana Beatriz Miranda De Sá ,&nbsp;Saulo Augusto Alves Da Cruz ,&nbsp;Sheila Espírito Santo Araújo ,&nbsp;Ana Maria Blanco Martinez ,&nbsp;Milena Batista Carneiro ,&nbsp;Henrique Rocha Mendonça","doi":"10.1016/j.neuro.2025.01.004","DOIUrl":"10.1016/j.neuro.2025.01.004","url":null,"abstract":"<div><div>Inflammatory demyelination is present in debilitating diseases such as Multiple Sclerosis (MS). Several drugs are available for MS treatment, with fingolimod as a first-line oral option in the United States. However, a cure has yet to be established, and therapeutic failures are common, highlighting the need for continued research into new pharmacological targets. Pranlukast has shown positive effects on myelination in cell cultures and after LPC-induced demyelination in mice, but it is not yet part of the therapeutic arsenal for this disease. This study investigates pranlukast’s effect on demyelination protection in an MS animal model, compared to fingolimod. For this purpose, young adult Swiss mice were treated for five weeks with a 0.2 % cuprizone diet and received daily intraperitoneal injections of pranlukast (0.1 mg/kg), fingolimod (1 mg/kg), or vehicle. Pranlukast treatment, like fingolimod, partially preserved sensory function in the tactile sensitivity test. Both treatments partially preserved myelin basic protein (MBP) levels, but only fingolimod preserved lipids and myelinated fibers in the corpus callosum (CC) at all g-ratio ranges. Cuprizone and Pranlukast groups presented more microglia/macrophages in the CC, but fewer presenting reactive microglia/macrophages and less NOS2 staining in pranlukast-treated when compared to the cuprizone group, while fingolimod treatment prevented the increase in Iba1 in the CC. In summary, this study demonstrated that pranlukast is a good candidate as a novel drug for use in conditions of inflammatory demyelination, such as MS, by restoring function through modulation of the inflammatory environment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"107 ","pages":"Pages 37-52"},"PeriodicalIF":3.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080649","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}