Neurotoxicology最新文献

{"title":"THC, CBD and minor cannabinoid CBDV differently modulate hippocampal neurons firing","authors":"Giulia Tomagra ,&nbsp;Nikita Gandlevskiy ,&nbsp;Elena Rosso ,&nbsp;Monica Bonardi ,&nbsp;Arianna Binello ,&nbsp;Valentina Carabelli ,&nbsp;Alessandro Barge","doi":"10.1016/j.neuro.2025.04.004","DOIUrl":"10.1016/j.neuro.2025.04.004","url":null,"abstract":"<div><div><em>Cannabis sativa</em> L. presents a very complex composition that includes several secondary metabolites besides the two main compounds, Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). Many of these minor cannabinoids are still under investigation and are arousing increasing interest for their biological effects and potential therapeutic roles. <em>Cannabis sativa</em> extracts, either properly purified and enriched with cannabinoids, were tested here on the neuronal activity, by monitoring the spontaneous firing rate and the bursts generation of cultured hippocampal neurons. In particular, we focused on the combined effect of THC, CBD and cannabidivarin (CBDV), a non-psychoactive homologue of CBD whose side chain has two fewer carbon atoms, and their related standard compounds. We found that standard THC, recognised for its psychoactive impact and side effects including anxiety and paranoia, significantly decreased the spontaneous firing discharge of cultured hippocampal neurons, whether applied alone or in combination with standard CBD at comparable concentrations. In contrast, the firing activity did not exhibit any significant alterations when CBD was administered alone. When <em>C. sativa</em> extracts were tested, we found that CBDV was able to reverse the inhibition of the firing discharge caused by the mixture of THC and CBD. Furthermore, when administered alone, CBDV significantly increased the firing discharge of hippocampal neurons. In all tested conditions, the effects exerted by standard compounds or extracts were restored to control conditions after 24 hours from administration. Overall, these data unravel a novel action of CBDV in reverting the detrimental effect exerted by the THC+CBD on neuronal firing activity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 180-190"},"PeriodicalIF":3.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815007","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":"Lead exposure, peripheral neurotransmitter levels and cognitive control: A neurobehavioral study in children from Montevideo, Uruguay","authors":"Gabriel Barg ,&nbsp;Juan Andrés Menéndez ,&nbsp;Juan Andrés Friedl ,&nbsp;Sandra Hoyos ,&nbsp;Elena I. Queirolo ,&nbsp;Nelly Mañay ,&nbsp;Diala Ghazal ,&nbsp;Katarzyna Kordas","doi":"10.1016/j.neuro.2025.03.009","DOIUrl":"10.1016/j.neuro.2025.03.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Lead exposure has been linked to significant brain disruptions. However, research on the neural correlates of blood lead level (BLL) and cognitive control remains limited. To address this gap, we investigated event-related potentials (ERPs) during an inhibition task, in conjunction with measurements of serum neurotransmitter availability.</div></div><div><h3>Method</h3><div>38 children (58 % girls) aged 9–13 years were evaluated using a go/no-go task. Total hits, commission and omission errors were registered. During the task, ERPs were recorded using a 59-channel array. BLL was measured using atomic absorption via flame or graphite furnace ionization techniques. In an exploratory approach, serum level of neurochemical factors such as BDNF, dopamine, serotonin, and GABA in serum were assessed using enzyme-linked immunosorbent assays.</div></div><div><h3>Results</h3><div>Median BLL was 1.00 µg/dL (IQR = 0.7, 1.7). In generalized linear regression models with Poisson distribution, BLL was associated with a 23 % higher commission errors (IRR [95 % CI] = 1.23 [1.14, 1.34]) and 16 % (1.16 [1.08, 1.22]) total omission errors after adjustment for age, sex, maternal education and hemoglobin level. Two ERPs linked to conflict monitoring (N2) and response inhibition (P3) showed positive, although non-significant, modulation by BLL. Regarding the neurotransmitters, dopamine was correlated with BLL particularly when measured concurrently (Spearman's rho = 0.51, p &lt; 0.005)</div></div><div><h3>Conclusions</h3><div>BLL are associated with deficits in the inhibition of prepotent responses during pre-adolescence. Such failures can hinder academic and social development and increase risky behaviors. This study is the first to examine peripheral neurotransmitter levels and brain activity associated with cognitive control in Pb-exposed children.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 159-168"},"PeriodicalIF":3.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796025","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":"PRDX1 affects acrylamide-induced neural damage through the PTEN/AKT signaling pathway","authors":"Dong-Xue Fu ,&nbsp;Ya-Ting Lei ,&nbsp;Hai-Bo Guo ,&nbsp;Ting Chen ,&nbsp;Xiang-Ying Gao ,&nbsp;Xiao-Li Wang ,&nbsp;Xiang Huang ,&nbsp;Ling-Ling Song ,&nbsp;Sheng-Yuan Wang ,&nbsp;Qin-Xue Dai","doi":"10.1016/j.neuro.2025.04.003","DOIUrl":"10.1016/j.neuro.2025.04.003","url":null,"abstract":"<div><div>Peroxiredoxin 1 (PRDX1) is a member of the peroxidase family of antioxidant enzymes. However, the role and mechanism of PRDX1 in acrylamide (ACR)-induced nerve damage have not been reported. We used SD rats and well-differentiated rat pheochromocytoma cells (PC-12 cells) to established <em>in vivo</em> and <em>in vitro</em> models of ACR. Immunohistochemistry, immunofluorescence and RT-qPCR experiments were used to detect the expression of PRDX1 in neurons of rat hippocampal tissue. The ultrastructural changes of neurons and PC-12 cells in rat hippocampal tissue were observed under transmission electron microscope. Western blot detected the protein expression levels of PRDX1, PTEN, AKT and p-AKT. <em>In vivo</em> and <em>in vitro</em> experimental results showed that PRDX1 showed a significant up-regulation trend after ACR exposure (<em>p</em> &lt; 0.05). <em>In vitro</em> experiments showed that after inhibiting PRDX1 expression with PRDX1 siRNA, the survival rate of PC-12 cells significantly increased, and the damage to cell morphology and organelles was markedly improved. Western blot analysis revealed that ACR exposure can cause a significant increase in PTEN protein expression level and p-AKT/AKT protein ratio (<em>p</em> &lt; 0.05). After inhibiting the expression of PRDX1, the protein expression level of PTEN and the protein ratio of p-AKT/AKT were significantly reduced, while the protein levels of SYN1 and BDNF were significantly increased (<em>p</em> &lt; 0.05). This study, for the first time, demonstrates that PRDX1 affects ACR-induced neurotoxicity by regulating the PTEN/AKT signaling pathway. And, provides novel insights into the prevention and treatment of neurotoxicity in populations exposed to ACR.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 150-158"},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792337","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 concentrations of glyphosate through direct or parental exposure alter nervous system development and reduce the fertility rate in zebrafish","authors":"Luis Terrazas-Salgado ,&nbsp;Miguel Betancourt-Lozano ,&nbsp;Alejandra García-Gasca ,&nbsp;Isabel Alvarado-Cruz","doi":"10.1016/j.neuro.2025.04.002","DOIUrl":"10.1016/j.neuro.2025.04.002","url":null,"abstract":"<div><div>N-(phosphonomethyl)glycine (glyphosate) is the most widely used herbicide worldwide. Although it has been extensively studied, few studies use realistic environmental concentrations to assess its potential effects on fish embryos and larvae. This work aims to evaluate potential neurotoxic and reproductive effects of realistic concentrations of glyphosate in non-target aquatic species using zebrafish larvae. Biological and reproductive biomarkers (condition factor, hepatic and gonadic indices, and fertility rate) were evaluated for adults exposed to 0, 10, 100, and 1000 µg/L, while a transcriptomic comparison was carried out for larvae from both exposure scenarios at 1000 µg/L. The fertility rate of exposed parents decreased with increasing glyphosate concentration, while gonadosomatic (GSI) and hepatosomatic (HIS) indices of females treated with 100 µg/L glyphosate were significantly higher in glyphosate-exposed fish compared to the control group; however, glyphosate treatment did not significantly change GSI or HSI in males. Transcriptomic analysis in larvae showed that glyphosate could alter developmental and metabolic processes, targeting the nervous system in both exposure schemes. The ability of glyphosate to alter the development of the nervous system in larvae of exposed parents suggests that exposure to gametes could produce intergenerational alterations, with potential ecotoxicological implications that remain to be determined.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 169-179"},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788316","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 effect of wildfire smoke exposure on student performance: A nationwide study across two decades (2000–2020) and over 40 million students in Brazil","authors":"Thiago N. Gardin,&nbsp;Weeberb J. Requia","doi":"10.1016/j.neuro.2025.03.005","DOIUrl":"10.1016/j.neuro.2025.03.005","url":null,"abstract":"<div><div>The impact of wildfire smoke exposure on public health has been extensively studied, yet its potential consequences on academic performance remain relatively unexplored, particularly in the context of fire-prone regions, such as Brazil. We conducted a nationwide study of more than 40 million high school students in Brazil who took the National High School Exam (ENEM) between 2000 and 2020. We used mixed-effects regression models with state-specific random intercepts to examine the associations between the wildfire events and academic performance among Brazilian students. We accounted for multiple covariates, including socioeconomic status, spatiotemporal factors, air pollutants, and weather variables. We also explored the effect modification by exam subject (general subjects and essay), school management (private and public schools), location (urban and rural schools), and time period. Our findings suggest that increased wildfire events are associated with lower academic performance in both essay and general subjects. After adjustments for the covariates, the primary analysis results indicate a negative impact of wildfires on essay writing, with an estimated coefficient of −0.09 (95 % CI: −0.13; −0.05) with 100 wildfire records increase. Similarly, an increase of 100 wildfire records per year corresponded to a decrease of 0.10 (95 % CI: 0.06; 0.11) points for general subjects. This effect on academic performance was associated with a reduction of 0.33 % (95 %CI: 0.31 %; 0.34 %) in essay and 0.54 % (95 %CI: 0.52 %; 0.56 %) in general subjects. Our findings highlight the need for further attention to the influence of wildfire smoke exposure on student academic performance, suggesting that even small associations at the individual level could have broader implications for public health and education policies.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 143-149"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692808","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":"Does healthy lifestyle attenuate the associations of phthalates with depression? A cross-sectional study","authors":"Yue He,&nbsp;Yan Xu,&nbsp;Chengxiang Hu,&nbsp;Lina Jin","doi":"10.1016/j.neuro.2025.03.008","DOIUrl":"10.1016/j.neuro.2025.03.008","url":null,"abstract":"<div><div>Phthalates have raised concerns on health outcomes including depression, due to its ubiquity. Knowledge is lacking on the role of modifiable lifestyle in attenuating phthalates’ adverse effects. We aimed to evaluate the interaction effects of lifestyle with urinary phthalate metabolites (UPMs) on depression. A total of 3588 participants aged ≥ 20 from the National Health and Nutrition Examination Survey 2011–2018 were involved. We used multivariate logistic regression models and Bayesian Kernel Machine Regression models to evaluate the associations of UPMs (individual or mixture) and lifestyle with depression. Positive associations of individual UPMs and its mixture with depression were observed in total population and participants maintaining an unfavorable lifestyle. No such association was found in participants with a healthy lifestyle. Interactions between lifestyle category with MECPP (<em>P</em> for interaction = 0.028), and ΣDEHP (<em>P</em> for interaction = 0.087) on depression were observed. Additionally, smoking, alcohol consumption and physical activity in healthy levels showed the greatest effect against depression among the common lifestyle combinations. In conclusion, positive associations of UPMs with depression risk, and interaction effects of lifestyle and UPMs on depression were observed. Our findings indicate that healthy lifestyle might weaken the adverse effects of phthalate exposure on depression risk.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 134-142"},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685452","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 combined effects of HSV-1 glycoprotein D and aluminum hydroxide on human neuroblastoma cells: Insights into oxidative DNA damage, apoptosis, and epigenetic modifications","authors":"Deniz Arca Çakır ,&nbsp;Anıl Yirün ,&nbsp;Selinay Başak Erdemli-Köse ,&nbsp;Göksun Demirel ,&nbsp;Jülide Secerli ,&nbsp;Merve Güdül-Bacanlı ,&nbsp;Pınar Erkekoğlu","doi":"10.1016/j.neuro.2025.03.007","DOIUrl":"10.1016/j.neuro.2025.03.007","url":null,"abstract":"<div><div>Herpes simplex virus type 1 (HSV-1) infections are a significant global health concern due to the virus's ability to evade apoptosis and establish lifelong latency in the peripheral nervous system. The specific viral components responsible for these effects remain unclear, necessitating individual examination of their molecular impacts. This study focused on investigating the effects of recombinant HSV-1 glycoprotein D (HSV-1 gD), a viral protein essential for host cell entry, and/or aluminum hydroxide, a known neurotoxic agent, on reactive oxygen species (ROS) production, apoptotic markers, and epigenetic modifications in SH-SY5Y neuroblastoma cells. Using inhibitory concentration 20 (IC₂₀) values for HSV-1 gD and aluminum hydroxide, experimental groups were established. Intracellular ROS levels, oxidative DNA damage, and the expression and activity of key apoptotic proteins were measured. Additionally, global DNA methylation, histone H3 and H4 acetylation, and the activities of histone deacetylases (HDAC3 and HDAC8) were evaluated. Results of the study showed that both HSV-1 gD and aluminum hydroxide independently increased ROS production and induced apoptosis in SH-SY5Y cells. Notably, significant alterations in epigenetic markers were observed, including decreased global DNA methylation and histone acetylation levels. These epigenetic modifications suggest potential underlying mechanisms for the neurotoxic effects of aluminum hydroxide and HSV-1 gD. In addition to the traditional suggestions for HSV-1 gD as an anti-apoptotic factor, our findings indicate that it may also contribute to neurotoxicity. This study provides new insights into the molecular interactions between viral components and neurotoxic agents and emphasizes the importance of epigenetic regulation in neuronal cell death.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 123-133"},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670322","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":"Effects of daily exposure to pyrethroid pesticides during infancy on children neurodevelopment at age four: A prospective study in rural Yunnan, China","authors":"Jirong Li ,&nbsp;Xiaoxiao Song ,&nbsp;Tong Luo ,&nbsp;Kek Khee Loo ,&nbsp;Shuqi Chen ,&nbsp;Tengwei Gui ,&nbsp;Xia Xiao ,&nbsp;Yan Li","doi":"10.1016/j.neuro.2025.03.006","DOIUrl":"10.1016/j.neuro.2025.03.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Exposure to pyrethroid pesticides (PYRs) of children in infancy at ages 1 and 2 may affect their neurodevelopmental outcomes at age 4.</div></div><div><h3>Objectives</h3><div>The study aimed to explore the longitudinal association of infancy PYRs exposure with neurodevelopment at age 4.</div></div><div><h3>Methods</h3><div>This study based on Xuanwei birth cohort study that started from January 2016 in rural Yunnan, China. Urine samples (n = 263) at ages 1 and 2 were tested for PYRs metabolites 3-phenoxybenzoic acid (3-PBA), 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA). PYRs metabolites were classified as low and high exposure using the 75th percentile values. Neurodevelopment of children aged 4 was assessed by Griffiths Development Scales-Chinese Edition (GDS-C). The development quotient below 85 was defined as low development level. Multiple linear regression and logistic regression were used to analyze the association of children’s PYRs exposure with their neurodevelopmental outcomes.</div></div><div><h3>Results</h3><div>Children’s PYRs metabolites detection rates were 98.48 % in infants at both age 1 and 2. The average levels of 3-PBA, 4-F-3-PBA and DBCA were 0.51 µg/L, 0.30 µg/L and &lt; 0.09 µg/L, respectively at age 1; and 0.88 µg/L, 0.82 µg/L, and 0.52 µg/L at age 2. The levels of three metabolites in 2-year-olds were higher than those in 1-year-olds. The children aged 4 had a general developmental quotient of 90.87 ± 11.37, with 28.14 % classified in low development level. Multiple linear regression analysis showed that higher 3-PBA level at 2-year-old was negatively associated with the quotient in locomotor (<em>β</em>=-14.61, <em>95 % CI:</em> −24.93, −4.30) and language (<em>β</em>=-10.89, <em>95 % CI:</em> −19.38, −2.41). Logistic regression displayed that higher 3-PBA level aged 2 was positively correlated with low development level in the language domain (<em>OR</em>=3.23, <em>95 % CI:</em> 1.33, 7.83), but negatively correlated with personal social domain (<em>OR</em>=0.23, 95 % <em>CI:</em> 0.07, 0.79).</div></div><div><h3>Conclusion</h3><div>Children were widely exposed to PYRs in infancy, which may impact on their neurodevelopment at age 4. Age 2 may be a sensitive window when PYRs exposure may negatively impact locomotor and language development. This study suggests that PYRs exposure should be minimized or avoided in child care, especially in children aged 2 years.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 105-112"},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625480","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 protective effect of Fingolimod upon visual behavior in a demyelination animal model is associated with synaptopathy prevention","authors":"Ana Carolina de Pádua ,&nbsp;Saulo Augusto Alves da Cruz ,&nbsp;Luiza dos Santos Heringer ,&nbsp;Greice Nascimento Pires ,&nbsp;Daniel Areias da Silva Raquita ,&nbsp;Jéssica dos Santos Tavares ,&nbsp;Pedro Souto Rodrigues ,&nbsp;Ana Beatriz Miranda de Sá ,&nbsp;Cintia Monteiro de Barros ,&nbsp;Sérgio Henrique Seabra ,&nbsp;Henrique Rocha Mendonça ,&nbsp;Renato Augusto DaMatta ,&nbsp;Sheila Espírito-Santo","doi":"10.1016/j.neuro.2025.03.004","DOIUrl":"10.1016/j.neuro.2025.03.004","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS that causes motor, cognitive, and sensory dysfunctions, with visual disorder being one of the most prevalent. Synaptopathy has been recognized as one of the predominant pathogenic components of MS. We previous characterized inhibition of synaptopathy in the visual thalamus using the cuprizone-induced demyelination MS animal model. However, investigations about potential treatments to prevent synaptopathy have received little attention. Fingolimod is one of the most widely used and effective immunomodulators for controlling inflammatory relapses in MS, but few studies in MS animal models have tested its effect on synaptopathy. Given that none of these investigations used the cuprizone-induced demyelination model, our study investigated the preventive effect of Fingolimod on cuprizone-induced synaptopathy. Using Western blotting for synaptophysin, PSD-95, and gephyrin, as well as ultrastructural analysis, we demonstrated that daily intraperitoneal injections of Fingolimod (1 mg/Kg) protect against the increase of inhibitory synapses in cuprizone-treated mice. Fingolimod also prevented reduction of ARC immunolabeling, a sensor of neuronal activity, in cuprizone animals. Finally, through the visual Cliff test, Fingolimod was able to protect cuprizone animals against visual dysfunction. On the other hand, through immunostaining for CNPase, GFAP and IBA-1 we observed that Fingolimod failed to prevent demyelination and glial reactivity in the cuprizone animals. Taken together, the data indicate the potential of preventive treatment with Fingolimod against synaptopathy and visual dysfunction associated with inflammatory demyelination.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 113-122"},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630688","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":"Neuronal degeneration, mitochondrial dysfunction, and disturbance of movements induced by rotenone in the ascidian Styela plicata","authors":"Nathany da Silva Nogueira ,&nbsp;Taynan Motta Portal ,&nbsp;Thuany da Silva Nogueira ,&nbsp;Aurenita Emile Sá Miranda ,&nbsp;Eldo Campos ,&nbsp;Cintia Monteiro de Barros","doi":"10.1016/j.neuro.2025.03.003","DOIUrl":"10.1016/j.neuro.2025.03.003","url":null,"abstract":"<div><div>Parkinson's disease (PD), a movement disorder caused by dopaminergic degeneration in the midbrain, has been induced in various organisms after injection of different neurotoxins, such as rotenone (ROT), which affect mitochondrial complex I. Due to the conserved characteristics of ascidians, these animals constitute an interesting model for comparative and genetic studies of neurodegenerative diseases. In this study, we investigated the effects of ROT on the ascidian nervous system, evaluating apoptosis, catecholaminergic enzymes, behavioral deficits, and mitochondrial dysfunction. The study revealed morphological disorganization, inducing vacuolation in the ascidian brain. Neuronal death was confirmed by elevated transcriptional levels of caspase-3 and intense caspase-3 staining by immunofluorescence. In addition, there was reduced staining for dopa-decarboxylase (DDC), which is involved in dopamine biosynthesis. Furthermore, the mitochondria exhibited dysfunction in their membrane potential, followed by a decrease in the hydrolytic activity of ATP synthase and high transcriptional levels of ubiquitin. Finally, after administration of the drug l-3,4-dihydroxyphenylalanine (L-DOPA), recovery of motor movements was observed, as revealed by behavioral tests. Overall, the current research provides new data on the effects of rotenone on the ascidian brain, inducing neuronal death, mitochondrial dysfunction, and siphon movement disorders in the ascidian <em>Styela plicata</em>.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 69-80"},"PeriodicalIF":3.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610617","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}