Neurotoxicology最新文献

{"title":"In vitro cytotoxicity assessment of ruxolitinib on oligodendrocyte precursor cell and neural stem/progenitor cell populations","authors":"Cheng-Wei Lim ,&nbsp;Gen Hamanaka ,&nbsp;Anna C. Liang ,&nbsp;Su Jing Chan ,&nbsp;King-Hwa Ling ,&nbsp;Eng H. Lo ,&nbsp;Ken Arai ,&nbsp;Pike See Cheah","doi":"10.1016/j.neuro.2024.08.004","DOIUrl":"10.1016/j.neuro.2024.08.004","url":null,"abstract":"<div><p>JAK-STAT signaling cascade has emerged as an ideal target for the treatment of myeloproliferative diseases, autoimmune diseases, and neurological disorders. Ruxolitinib (Rux), is an orally bioavailable, potent and selective Janus-associated kinase (JAK) inhibitor, proven to be effective to target activated JAK-STAT pathway in the diseases previously described. Unfortunately, limited studies have investigated the potential cytotoxic profile of Rux on other cell populations within the heterogenous CNS microenvironment. Two stem and progenitor cell populations, namely the oligodendrocyte precursor cells (OPCs) and neural stem/progenitor cells (NSPCs), are important for long-term maintenance and post-injury recovery response of the CNS. In light of the limited evidence, this study sought to investigate further the effect of Rux on proliferating and differentiating OPCs and NSPCs populations. In the present study, cultured rat OPCs and NSPCs were treated with various concentrations of Rux, ranging from 2 μM to 20 μM. The effect of Rux on proliferating OPCs (PDGF-R-α⁺) and proliferating NSPCs (nestin⁺) was assessed via a 3-day Rux treatment, whereas its effect on differentiating OPCs (MBP⁺/PDGF-R-α⁺) and differentiating NSPCs (neurofilament⁺) was assessed after a 7-day treatment. Cytotoxicity of Rux was also assessed on OPC populations by examining its influence on cell death and DNA synthesis via YO-PRO-1/PI dual-staining and BrdU assay, respectively. The results suggest that Rux at a dosage above 10 μM reduces the number proliferating OPCs, likely via the induction of apoptosis. On the other hand, Rux treatment from 2.5 μM to 20 μM significantly reduces the number of differentiating OPCs by inducing necrosis. Meanwhile, Rux treatment has no observable untoward impact on NSPC cultures within the dosage range tested. Taken together, OPCs appears to be more vulnerable to the dosage effect of Rux, whereas NSPCs are not significantly impacted by Rux, suggesting a differential mechanism of actions of Rux on the cell types.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"105 ","pages":"Pages 10-20"},"PeriodicalIF":3.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095544","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":"Use of phytocanabinoids in animal models of Parkinson's disease: Systematic review","authors":"Amanda de Deus Ferreira Alves ,&nbsp;Fernanda Carolina Ribeiro Dias ,&nbsp;Pabyton Gonçalves Cadena ,&nbsp;Valdemiro Amaro Silva-Jr","doi":"10.1016/j.neuro.2024.08.002","DOIUrl":"10.1016/j.neuro.2024.08.002","url":null,"abstract":"<div><p>This systematic review was carried out with the aim of evaluating the use of medicinal Cannabis for the treatment of Parkinson's disease in experimental models. Furthermore, we sought to understand the main intracellular mechanisms capable of promoting the effects of phytocannabinoids on motor disorders, neurodegeneration, neuroinflammation and oxidative stress. The experimental models were developed in mice, rats and marmosets. There was a predominance of using only males in relation to females; in three studies, the authors evaluated treatments in males and females. Drugs were used as inducers of Parkinson's disease: 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), lipopolysaccharide (LPS), and rotenone. Substances capable of promoting catalepsy in animals were also used: haloperidol, L-nitro-N-arginine (L-NOARG), WIN55,212–2, and reserpine. The inducing agent was injected stereotaxically or intraperitoneally. The most commonly used treatments were cannabidiol (CBD), Delta-9-tetrahydrocannabinol (Δ-9 THC) and Delta-9-tetrahydrocannabivarin (Δ-9 THCV), administered intraperitoneally, orally, subcutaneously and intramuscularly. The use of phytocannabinoids improved locomotor activity and involuntary movement and reduced catalepsy. There was an improvement in the evaluation of dopaminergic neurons, while in relation to dopamine content, the treatment had no effect. Inflammation, microglial/astrocyte activation and oxidative stress were reduced after treatment with phytocannabinoids, the same was observed in the results of tests for allodynia and hyperalgesia.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"105 ","pages":"Pages 34-44"},"PeriodicalIF":3.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056166","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":"Sevoflurane promotes neuronal ferroptosis via upregulation of PLIN4 to modulate the hippo signaling pathway","authors":"Fei Zeng ,&nbsp;Mingxia Zhou ,&nbsp;Qiang Li ,&nbsp;Huan Hu ,&nbsp;Chen Chen","doi":"10.1016/j.neuro.2024.08.001","DOIUrl":"10.1016/j.neuro.2024.08.001","url":null,"abstract":"<div><h3>Background</h3><p>Sevoflurane is a widely used inhalation anesthetic associated with neuronal damage, cognitive impairment and neurodegenerative diseases, with iron overload reported to contribute to these adverse effects. However, the mechanisms of iron-dependent cell death (ferroptosis) in sevoflurane-induced neurotoxicity remain poorly understood.</p></div><div><h3>Methods</h3><p>The role of PLIN4, a protein associated with neurodegeneration, in sevoflurane-induced neuronal damage was investigated using cultured mouse hippocampal neurons (HT22). PLIN4 knockdown or overexpression was performed through vector transfection, and PLIN4 transcription and expression levels after sevoflurane treatment and knockdown experiments were assessed via RT-qPCR, immunostaining, and western blot to evaluate its impact on ferroptosis. Transmission electron microscopy was used to assess cellular morphology and measure Fe²⁺ levels.</p></div><div><h3>Results</h3><p>Sevoflurane treatment significantly increased PLIN4 expression in hippocampal neurons and induced ferroptosis. Silencing PLIN4 reduced ferroptosis and partially reversed sevoflurane's inhibition of the Hippo signaling pathway. Specifically, sevoflurane treatment led to a 2.9-fold increase in PLIN4 mRNA levels. Furthermore, higher PLIN4 levels upregulated ferroptosis in hippocampal neurons by inhibiting the Hippo pathway.</p></div><div><h3>Conclusion</h3><p>Our study indicates that sevoflurane promotes ferroptosis in neurons by upregulating PLIN4 and modulating the Hippo signaling pathway. These findings provide insights into the potential development of interventions to prevent anesthesia-related cognitive impairments and neurodegeneration.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"105 ","pages":"Pages 1-9"},"PeriodicalIF":3.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056142","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":"Long-term exposure to ionic liquid [C8mim]Br induces the potential risk of anxiety and memory deterioration through disturbing neurotransmitter systems","authors":"Huangyingzi Wang ,&nbsp;Xuhua Li ,&nbsp;Jun Li ,&nbsp;Fan Yu ,&nbsp;Qi Li ,&nbsp;Mijia Qin ,&nbsp;Lin Gui ,&nbsp;Yajie Qian ,&nbsp;Manhong Huang","doi":"10.1016/j.neuro.2024.07.014","DOIUrl":"10.1016/j.neuro.2024.07.014","url":null,"abstract":"<div><p>1-octyl-3-methylimidazolium bromide ([C₈mim]Br), one of the ionic liquids (ILs), has been used in various fields as an alternative green solvent of conventional organic solvents. Increased application and stabilization of imidazole ring structure lead to its release into the aquatic environment and long-term retention. Structure-activity relationship consideration suggested that ILs may be acetylcholinesterase inhibitors; however, neurotoxicity in vivo, especially the underlying mechanisms is rarely studied. In this study, the zebrafish were exposed to 2.5–10 mg/L [C₈mim]Br for 28 days to comprehensively evaluate the neurotoxicity of ILs on adult zebrafish from the behavioral profiles and neurotransmitter systems for the first time. The results indicate that zebrafish exhibit suppressed spatial working memory and anxious behaviors. To assess the potential neurotoxic mechanisms underlying the behavioral responses of zebrafish, we measured the levels of neurotransmitters and precursors, key enzyme activities, and expression levels of relevant genes. Nissl staining showed significant neural cell death in zebrafish after 28-day [C₈mim]Br exposure, with corresponding decreases in the levels of neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptophan, gamma-aminobutyric acid, dopamine, and norepinephrine). Furthermore, these results were associated with mRNA expression levels of the disrupted neurotransmitter key genes (<em>th</em>, <em>tph2</em>, <em>mao</em>, <em>slc6a3</em>, <em>ache</em>, <em>gad67</em>). Overall, our study determined that [C₈mim]Br caused potential mental disorders like anxiety and memory deterioration in zebrafish by impairing neurotransmitter systems, providing recommendations for the industrial production and application of [C₈mim]Br.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 66-74"},"PeriodicalIF":3.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860380","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":"AOP-based framework for predicting the joint action mode of di-(2-ethylhexyl) phthalate and bisphenol A co-exposure on autism spectrum disorder","authors":"Kanglong Cui ,&nbsp;Ludi Li ,&nbsp;Kai Li ,&nbsp;Wusheng Xiao ,&nbsp;Qi Wang","doi":"10.1016/j.neuro.2024.07.012","DOIUrl":"10.1016/j.neuro.2024.07.012","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD), also known as autism, is a common, highly hereditary and heterogeneous neurodevelopmental disorder. The global prevalence of ASD among children continues to rise significantly, which is partially attributed to environmental pollution. It has been reported that pre- or post-natal exposure to di-(2-ethylhexyl) phthalate (DEHP) or bisphenol A (BPA), two prevalent environmental endocrine disruptors, increases the risk of ASD in offspring. Yet, the joint action mode linking DEHP and BPA with ASD is incompletely understood. This study aims to unravel the joint action mode of DEHP and BPA co-exposure on the development of ASD. An adverse outcome pathway (AOP) framework was employed to integrate data from multiple public database and construct chemical-gene-phenotype-disease networks (CGPDN) for DEHP- and BPA-related ASD. Topological analysis and comprehensive literature exploration of the CGPDN were performed to build the AOP. By analysis of shared key events (KEs) or phenotypes within the AOP or the CGPDN, we uncovered two AOPs, decreased N-methyl-D-aspartate receptor (NMDAR) and estrogen antagonism that were likely linked to ASD, both with moderate confidence. Our analysis further predicted that the joint action mode of DEHP and BPA related ASD was possibly an additive or synergistic action. Thus, we propose that the co-exposure to BPA and DEHP perhaps additively or synergistically increases the risk of ASD.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 75-84"},"PeriodicalIF":3.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860379","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 exposure to arsenic reduces anxiety levels and leads to a depressive-like behavior in female offspring rats: Molecular changes in the prefrontal cortex","authors":"Mariana Bartos ,&nbsp;Cristina E. Gallegos ,&nbsp;Nina Mónaco ,&nbsp;Ileana Lencinas ,&nbsp;Sergio Dominguez ,&nbsp;Cristina Bras ,&nbsp;María del Carmen Esandi ,&nbsp;Cecilia Bouzat ,&nbsp;Fernanda Gumilar","doi":"10.1016/j.neuro.2024.07.013","DOIUrl":"10.1016/j.neuro.2024.07.013","url":null,"abstract":"<div><p>Exposure to inorganic arsenic (iAs) detrimentally affects the structure and function of the central nervous system. In-utero and postnatal exposure to iAs has been connected to adverse effects on cognitive development. Therefore, this investigation explores neurobehavioral and neurochemical effects of 0.05 and 0.10 mg/L iAs exposure during gestation and lactation periods on 90-day-old female offspring rats. The assessment of anxiety- and depressive-like behaviors was conducted through the application of an elevated plus maze and a forced swim test. The neurochemical changes were evaluated in the prefrontal cortex (PFC) through the determination of enzyme activities and α1 GABA_A subunit expression levels. Our findings revealed a notable impact of iAs exposure on anxiety and the induction of depressive-like behavior in 90-day-old female offspring. Furthermore, the antioxidant status within the PFC exhibited discernible alterations in exposed rats. Notably, the activities of acetylcholinesterase and glutamate pyruvate transaminase demonstrated an increase, while glutamate oxaloacetate transaminase activity displayed a decrease within the PFC due to the iAs treatment. Additionally, a distinct downregulation in the mRNA expression of the α1GABA_A receptor was observed in this neuronal region. These findings strongly suggest that iAs exposure during early stages of rat development causes significant modifications in brain oxidative stress markers and perturbs the activity of enzymes associated with cholinergic and glutamatergic systems. In parallel, it elicits a discernible reduction in the level of GABA receptors within the PFC. These molecular alterations may play a role in the diminished anxiety levels and the depressive-like behavior outlined in the current investigation.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 85-94"},"PeriodicalIF":3.4,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846861","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":"Association of plasma metals with resting-state functional connectivity in ischemic stroke","authors":"Xiaoxiao Song ,&nbsp;Jianxing Meng ,&nbsp;Jiale Li ,&nbsp;Bing Shen ,&nbsp;Jinling Li ,&nbsp;Miaomiao Xu ,&nbsp;Honghai Wang ,&nbsp;Lian Gu ,&nbsp;Yufei Wei","doi":"10.1016/j.neuro.2024.07.011","DOIUrl":"10.1016/j.neuro.2024.07.011","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Metal exposure has long been considered a significant risk factor for ischemic stroke. However, existing data on the effects of metal exposure on brain function in ischemic stroke are limited. Therefore, this study aimed to explore the correlation between exposure to various metals and changes in resting-state functional connectivity (rs-FC) in ischemic stroke patients.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;This study included 28 acute ischemic stroke patients with hemiplegia and 28 matched healthy controls (HCs). All participants underwent T1-weighted MRI and 3.0 T resting-state functional magnetic resonance imaging (fMRI). After MRI acquisition, the rs-FC between 137 cortical and subcortical regions was extracted and preprocessed. Plasma levels of 19 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). The Bayesian kernel machine regression (BKMR) model and the weighted quantile sum regression (WQS) model were used to assess the overall effect of metal mixture exposure. The severity of neurological deficits in each acute ischemic stroke patient was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Additionally, the associations between exposure to various metals and modifications in brain functional connectivity were determined using Pearson or Spearman correlation analysis.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Bilateral brain connectivity was significantly decreased compared to controls and was associated with neurological impairment in ischemic stroke. In patients with ischemic stroke, the plasma concentrations of Cr (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), Cu (&lt;em&gt;p&lt;/em&gt; = 0.004), As (&lt;em&gt;p&lt;/em&gt; = 0.010), Cs (&lt;em&gt;p&lt;/em&gt; = 0.046), Rb (&lt;em&gt;p&lt;/em&gt; = 0.041), and Sb (&lt;em&gt;p&lt;/em&gt; = 0.001) were significantly higher than those in the HCs, whereas the plasma Tl concentrations (&lt;em&gt;p&lt;/em&gt; = 0.022) were significantly lower. The results of the BKMR and WQS models showed that combined exposure to metal mixtures was linked to a higher risk of ischemic stroke. Cr was positively correlated with the rs-FC between the left Rolandic_Oper and the left Supp_Motor_Area (&lt;em&gt;r&lt;/em&gt; = 0.414, &lt;em&gt;p&lt;/em&gt; = 0.029), while negatively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal (&lt;em&gt;r&lt;/em&gt; = −0.398, &lt;em&gt;p&lt;/em&gt; = 0.037). Cu was negatively correlated with the rs-FC between the left paracentral lobule and the left thalamus (&lt;em&gt;r&lt;/em&gt; = −0.409, &lt;em&gt;p&lt;/em&gt; = 0.031). Tl was positively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal cortex (&lt;em&gt;r&lt;/em&gt; = 0.590, &lt;em&gt;p&lt;/em&gt; = 0.001). A negative correlation was observed between Cs and rs-FC between the right Cingulate_Mid and left Occipital_Sup (&lt;em&gt;r&lt;/em&gt; = −0.429, &lt;em&gt;p&lt;/em&gt; = 0.024). Sb was negatively correlated with the rs-FC between the left Parietal_Inf and the right SupraMarginal (&lt;em&gt;r&lt;/em&gt; = −0.384, &lt;em&gt;p&lt;/em&gt; = 0.044), the right Parietal_Inf and the left SupraMarginal (&lt;em&gt;r&lt;/em&gt; = −0.583, &lt;em&gt;p","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 56-65"},"PeriodicalIF":3.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766879","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":"Microglial responses to inflammatory challenge in adult rats altered by developmental exposure to polychlorinated biphenyls in a sex-specific manner","authors":"Katherine A. Walker ,&nbsp;Simone T. Rhodes ,&nbsp;Deborah A. Liberman ,&nbsp;Andrea C. Gore ,&nbsp;Margaret R. Bell","doi":"10.1016/j.neuro.2024.07.009","DOIUrl":"10.1016/j.neuro.2024.07.009","url":null,"abstract":"<div><p>Polychlorinated biphenyls are ubiquitous environmental contaminants linkedc with peripheral immune and neural dysfunction. Neuroimmune signaling is critical to brain development and later health; however, effects of PCBs on neuroimmune processes are largely undescribed. This study extends our previous work in neonatal or adolescent rats by investigating longer-term effects of perinatal PCB exposure on later neuroimmune responses to an inflammatory challenge in adulthood. Male and female Sprague-Dawley rats were exposed to a low-dose, environmentally relevant, mixture of PCBs (Aroclors 1242, 1248, and 1254, 1:1:1, 20 μg / kg dam BW per gestational day) or oil control during gestation and via lactation. Upon reaching adulthood, rats were given a mild inflammatory challenge with lipopolysaccharide (LPS, 50 μg / kg BW, <em>ip</em>) or saline control and then euthanized 3 hours later for gene expression analysis or 24 hours later for immunohistochemical labeling of Iba1+ microglia. PCB exposure did not alter gene expression or microglial morphology independently, but instead interacted with the LPS challenge in brain region- and sex–specific ways. In the female hypothalamus, PCB exposure blunted LPS responses of neuroimmune and neuromodulatory genes without changing microglial morphology. In the female prefrontal cortex, PCBs shifted Iba1+ cells from reactive to hyperramified morphology in response to LPS. Conversely, in the male hypothalamus, PCBs shifted cell phenotypes from hyperramified to reactive morphologies in response to LPS. The results highlight the potential for long-lasting effects of environmental contaminants that are differentially revealed over a lifetime, sometimes only after a secondary challenge. These neuroimmune endpoints are possible mechanisms for PCB effects on a range of neural dysfunction in adulthood, including mental health and neurodegenerative disorders. The findings suggest possible interactions with other environmental challenges that also influence neuroimmune systems.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 95-115"},"PeriodicalIF":3.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748701","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":"Rutin alleviates Pb-induced oxidative stress, inflammation and cell death via activating Nrf2/ARE system in SH-SY5Y cells","authors":"Fen Li ,&nbsp;Lin Zhang ,&nbsp;Xingxu Zhang ,&nbsp;Qimeng Fang ,&nbsp;Yingshun Xu ,&nbsp;Hui Wang","doi":"10.1016/j.neuro.2024.07.010","DOIUrl":"10.1016/j.neuro.2024.07.010","url":null,"abstract":"<div><p>Lead (Pb) is harmful to almost all organs, particularly the developmental neural system, and previous studies revealed oxidative stress played an important role in Pb neurotoxicity. Rutin, a type of flavonoid glycoside found in various plants and fruits, is widely used as a dietary supplement due to its antioxidant and anti-inflammatory properties, but whether rutin could protect against Pb neurotoxicity is unclear. In this study, we found rutin treatment significantly alleviated Pb-induced cell death, oxidative stress, and inflammation, resulting in cell survival. Moreover, rutin treatment promoted nuclear factor erythroid 2-related factor 2 (Nrf2) translocation from cytoplasm to nucleus and subsequently activated antioxidant and detoxifying enzymes expression including HO-1. Knocking down Nrf2 by siRNA transfection abolished this protection of rutin against Pb. Overall, rutin could alleviate Pb-induced oxidative stress, inflammation, and cell death by activating the Nrf2/antioxidant response elements (ARE) system.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 1-10"},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734727","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":"Tropospheric ozone effect on olfactory perception and olfactory bulb dopaminergic interneuron excitability","authors":"Angela Pignatelli ,&nbsp;Mascia Benedusi ,&nbsp;Mario Barbieri ,&nbsp;Alessandra Pecorelli ,&nbsp;Giuseppe Valacchi","doi":"10.1016/j.neuro.2024.07.003","DOIUrl":"10.1016/j.neuro.2024.07.003","url":null,"abstract":"<div><p>Ozone (O₃) forms in the Earth’s atmosphere, both naturally and by reactions of man-made air pollutants. Deleterious effects of O₃ have been found in the respiratory system. Here, we examine whether O₃ alters olfactory behavior and cellular properties in the olfactory system. For this purpose, mice were exposed to O₃ at a concentration found in highly polluted city air [0.8 ppm], and the behavior elicited by social and non-social odors in habituation/dishabituation tests was assessed. In addition, the electrical responses of dopaminergic olfactory bulb (OB) neurons were also evaluated. O₃ differentially compromises olfactory perception to odors: it reduces responses to social and non-social odors in Swiss Webster mice, while this effect was observed in C57BL/6 J mice only for some non-social odors. Additionally, O₃ reduced the rate of spontaneous spike firing in periglomerular dopaminergic cells (PG-DA) of the OB. Because this effect could reflect changes in excitability and/or synaptic inputs, the ability of O₃ to alter PG-DA spontaneous activity was also tested together with cell membrane resistance, membrane potential, rheobase and chronaxie. Taken together, our data suggest the ability of O₃ to affect olfactory perception.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"104 ","pages":"Pages 36-44"},"PeriodicalIF":3.4,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161813X24000755/pdfft?md5=842c416e847f2c4af5704364dee3832e&pid=1-s2.0-S0161813X24000755-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}