Daiana Alves Spilere, Guilherme Lodetti, Ana Carolina Salvador de Farias, Amanda Gomes Teixeira, Eduardo Ronconi Dondossola, Eduardo Pacheco Rico
{"title":"Effects of N-acetylcysteine after repeated exposure to ethanol in memory and neurotransmission in zebrafish","authors":"Daiana Alves Spilere, Guilherme Lodetti, Ana Carolina Salvador de Farias, Amanda Gomes Teixeira, Eduardo Ronconi Dondossola, Eduardo Pacheco Rico","doi":"10.1016/j.ntt.2025.107508","DOIUrl":"10.1016/j.ntt.2025.107508","url":null,"abstract":"<div><h3>Introduction</h3><div>In the brain, alcohol metabolites alter the functioning of several neurotransmission systems, such as glutamatergic and cholinergic, in addition to impairing memory and learning. Medications for Alcohol Use Disorders (AUD) cause adverse effects and contraindications. <em>N</em>-acetylcysteine (NAC) has been shown to protect memory and restore acetylcholinesterase (AChE) levels. Additionally, it functions as an antioxidant that works alongside glutathione, which is associated with the glutamatergic synapse. In this context, the current research aimed to examine the neuroprotective effects of NAC in animals that underwent repeated ethanol exposure (REE), along with the impacts on memory and the cholinergic and glutamatergic signaling pathways in zebrafish.</div></div><div><h3>Methods</h3><div>The animals were exposed to 1 % ethanol for 8 days for 20 min daily. They received treatment with NAC after the eighth exposure to ethanol for 10 or 60 min. Euthanasia occurred 24 h after the last exposure. Inhibitory avoidance and object recognition tests were performed. Also, the choline acetyltransferase (ChAT) enzyme activities, AChE activity, and glutamate uptake were evaluated.</div></div><div><h3>Results</h3><div>The results show a significant AChE activity increase in the REE group and a decrease in those exposed to alcohol and treated with NAC for 10 min. No significant differences were found regarding ChAT activity. REE significantly reduced glutamate uptake. All groups except the ethanol group acquired aversive memory in inhibitory avoidance tests. Only the NAC-treated group demonstrated longer new object exploration in the recognition test. The study indicates that REE affects AChE, glutamate uptake, and aversive memory and that a single NAC treatment can mitigate these effects. These findings enhance the understanding of REE mechanisms and NAC's protective properties against ethanol-induced damage in zebrafish.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"110 ","pages":"Article 107508"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294151","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}
Wenwen Jiang , Xixin Fan , Hui Wu , Jiankang Song , Chunhe Yang , Zhanzhi Zhao
{"title":"TREM2 inhibits LPS-induced pyroptosis and inflammation by promoting mitophagy via SYK in BV2 cells","authors":"Wenwen Jiang , Xixin Fan , Hui Wu , Jiankang Song , Chunhe Yang , Zhanzhi Zhao","doi":"10.1016/j.ntt.2025.107500","DOIUrl":"10.1016/j.ntt.2025.107500","url":null,"abstract":"<div><div>Neuroinflammation is a critical factor in the pathogenesis of postoperative cognitive dysfunction (POCD). Maintaining microglial homeostasis is vital for regulating neuroinflammation, as microglial cell death can trigger an inflammatory response within the central nervous system. The triggering receptor expressed on myeloid cells 2 (TREM2) plays an essential role in supporting cell survival and modulating microglial-driven neuroinflammation. Our previous study indicated that TREM2 overexpression exerts protective effects against neuroinflammation and cognitive deficits in aged mice. However, the precise mechanisms by which TREM2 functions in microglia remain unclear. Consequently, this study aimed to examine the role of TREM2 in lipopolysaccharide (LPS)-induced cell death and neuroinflammation in BV2 cells. This research showed that TREM2 reduces LPS-induced nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis and the subsequent release of inflammatory factors through western blot analysis, flow cytometry, and enzyme-linked immunosorbent assay. Recent research has suggested that the loss of spleen tyrosine kinase (SYK), a downstream receptor kinase of TREM2 in microglia, results in exacerbated neuroinflammatory disease. This study further demonstrated that SYK activation via TREM2 treatment exerts neuroprotective effects by mitigating LPS-induced mitochondrial membrane potential damage, facilitating mitophagy, and inhibiting NLRP3-mediated pyroptosis in BV2 cells. Conversely, SYK inhibition by R406 led to microglial cell death and aggravated neuroinflammation, thereby reducing the neuroprotective effects of TREM2. Our findings indicate that TREM2 and SYK mitigate the inflammatory response in LPS-induced BV2 microglia and interfere with pyroptosis by enhancing mitophagy. These findings suggest that TREM2 and SYK may be valuable therapeutic targets for neuroinflammation.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"110 ","pages":"Article 107500"},"PeriodicalIF":2.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208961","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}
Lynn Singer , Elizabeth Schultheis , Jeffrey Albert , June-yung Kim , Sonia Minnes , Meeyoung Min
{"title":"Pathways from prenatal alcohol exposure to adult working memory deficit","authors":"Lynn Singer , Elizabeth Schultheis , Jeffrey Albert , June-yung Kim , Sonia Minnes , Meeyoung Min","doi":"10.1016/j.ntt.2025.107483","DOIUrl":"10.1016/j.ntt.2025.107483","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107483"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297817","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":"Identifying teratogens: Challenges and opportunities","authors":"Sonja A. Rasmussen","doi":"10.1016/j.ntt.2025.107453","DOIUrl":"10.1016/j.ntt.2025.107453","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107453"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297619","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":"Identification of neurotoxicology (NT)/developmental neurotoxicology (DNT) adverse outcome pathways and key event linkages with in vitro DNT screening assays","authors":"Emily Pitzer","doi":"10.1016/j.ntt.2025.107459","DOIUrl":"10.1016/j.ntt.2025.107459","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107459"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297624","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}
Emily Pitzer, Tracey Beasley, Garyn Jung, Kathy McDaniel, William Padgett, Witold Winnik, David Herr
{"title":"Proteomic changes and pathway analysis of brain tissues following exposure to the glutamatergic excitotoxin, kainic acid in Long Evans rats","authors":"Emily Pitzer, Tracey Beasley, Garyn Jung, Kathy McDaniel, William Padgett, Witold Winnik, David Herr","doi":"10.1016/j.ntt.2025.107486","DOIUrl":"10.1016/j.ntt.2025.107486","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107486"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297680","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}
Charles Vorhees, Adam Fritz, Brooke Gollaway, Michael Williams
{"title":"Gene x environment interaction between heterozygous deletion of the ADHD risk gene latrophilin-3 (Lphn3) and developmental deltamethrin exposure in Sprague Dawley rats","authors":"Charles Vorhees, Adam Fritz, Brooke Gollaway, Michael Williams","doi":"10.1016/j.ntt.2025.107492","DOIUrl":"10.1016/j.ntt.2025.107492","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107492"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296969","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":"Reverse translation in animals and cell models: Methods to accelerate therapeutic development and mechanisms","authors":"Gregg Stanwood","doi":"10.1016/j.ntt.2025.107461","DOIUrl":"10.1016/j.ntt.2025.107461","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107461"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297613","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":"Constellation of traits of disorders? Challenging our definition of autism as an adverse outcome","authors":"Sura Alwan","doi":"10.1016/j.ntt.2025.107463","DOIUrl":"10.1016/j.ntt.2025.107463","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107463"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297615","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":"Work & family: How a social scientist thinks about chemical and non-chemical toxicants","authors":"Joseph Grzywacz","doi":"10.1016/j.ntt.2025.107464","DOIUrl":"10.1016/j.ntt.2025.107464","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"109 ","pages":"Article 107464"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297617","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}