Neurotoxicology最新文献

{"title":"Impact of a high-fat diet on spatial learning and memory: The role of sex, APOE genotype, and postnatal chlorpyrifos exposure","authors":"Laia Guardia-Escote ,&nbsp;Judit Biosca-Brull ,&nbsp;Jordi Blanco ,&nbsp;Maria Cabré ,&nbsp;Pia Basaure ,&nbsp;Cristian Pérez-Fernández ,&nbsp;Fernando Sánchez-Santed ,&nbsp;José L. Domingo ,&nbsp;Maria Teresa Colomina","doi":"10.1016/j.neuro.2025.07.004","DOIUrl":"10.1016/j.neuro.2025.07.004","url":null,"abstract":"<div><div>Environmental factors, such as exposure to neurotoxicants and diet, play a critical role in shaping cognitive function, particularly in genetically susceptible individuals. Chlorpyrifos (CPF), an organophosphate pesticide, and high-fat diets (HFD) have been independently associated with cognitive impairment, yet their combined effects remain poorly understood. Apolipoprotein E (<em>APOE)</em> genotype influences vulnerability to cognitive decline, with the <em>ε4</em> allele being a major risk factor for neurodegenerative diseases. This study assessed the interplay between <em>APOE</em> genotype, sex, early-life CPF exposure, and HFD on spatial learning and memory. Male and female C57BL/6, apoE3- and apoE4-targeted replacement (TR) mice were orally exposed to CPF during postnatal days 10–15 and subsequently subjected to a HFD for 8 weeks. At the end of the HFD challenge, body weight gain was calculated, and spatial learning and memory assessed using the Morris Water Maze test. Results indicate that HFD-driven weight gain was influenced by sex and <em>APOE</em> genotype. All groups acquired the spatial learning task, but postnatal CPF exposure affected performance in certain groups. Retention was more variable in females, suggesting increased susceptibility to environmental exposures. Notably, apoE4-TR females showed improved memory retention following either CPF exposure or HFD, whereas apoE4-TR males exhibited impaired long-term memory after HFD exposure. These findings highlight the complex interactions between genetic and environmental factors. Understanding these dynamics is essential for developing targeted nutritional and public health strategies to mitigate cognitive decline. Importantly, dietary recommendations should not be generalized but tailored to individual profiles to optimize cognitive health and disease prevention.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"110 ","pages":"Pages 42-52"},"PeriodicalIF":3.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626785","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":"cth-2/mpst-1-dependent H₂S deficiency enhances acrylonitrile acute toxicity in Caenorhabditis elegans.","authors":"Bobo Yang, Michael Aschner, Rongzhu Lu","doi":"10.1016/j.neuro.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.neuro.2025.07.002","url":null,"abstract":"<p><p>Acrylonitrile (AN) is a toxic, colorless to pale-yellow liquid extensively used in industrial production, has been linked to neurotoxicity. Though our previous study showed a correlation between AN-induced neurotoxicity and gasotransmitter hydrogen sulfide (H₂S) in mammalian cells, experimental evidence on overall animal toxicity and specific neurological injury is still limited. We aimed to further explore the molecular association between H₂S and AN-induced acute toxicity in Caenorhabditis elegans (C. elegans) by using its genetic advantages, and provide experimental evidence for the validation of H₂S donors as AN antidote. In the present study, we demonstrated that acute AN exposure resulted in toxicity as evidenced by changes in death rate, locomotor behavior, brood size, dopaminergic neuron morphology, and oxidative stress. Notably, AN inhibited the H₂S content, which was double-examined by methylene blue spectrophotometry and lead acetate paper assay. Furthermore, AN significantly decreased 3-mercaptopyruvate transferase (3-MPST)-mediated H₂S synthesizing activity and the transcription level of the corresponding coding gene mpst-1 but had no effect on the cystathionine β synthetase (CBS)/cystathionine γ lyase (CSE)-mediated H₂S synthesizing activity using L-cysteine as a common substrate and the mRNA levels of H₂S oxidative metabolism enzymes. cth-2 and mpst-1 mutations significantly downregulated the H₂S content and the corresponding H₂S synthesizing activity, and further enhanced the AN-induced toxicity response including lethality, brood size and lifespan. In contrast, H₂S donor GYY4137 significantly attenuated the AN-damaged survival rate, body bends, and dopaminergic neuron morphology. Our findings demonstrated that the reduction of H₂S mediates the acute toxicity of acrylonitrile.</p>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626784","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 role of nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and Nrf2 signalling in methanol-induced on brain, eye, and pancreas toxicity in rats","authors":"Meriam NN Rezk ,&nbsp;Mariem Maher Shafek Keryakous ,&nbsp;Michael A. Fawzy ,&nbsp;Fatma El-Zahraa A. Abd El-Aziz ,&nbsp;Asmaa F.A. Dawood ,&nbsp;Hanan D. Yassa ,&nbsp;Nermeen N. Welson","doi":"10.1016/j.neuro.2025.07.003","DOIUrl":"10.1016/j.neuro.2025.07.003","url":null,"abstract":"<div><div>Toxic methyl alcohol is widely employed in industry, and it is highly toxic. Only 15 cc ingestion can result in irreversible blindness. The mechanism of toxicity is still a matter of debate. This study was conducted to investigate the incorporation of nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and Nrf2 signaling pathways in the toxicity of the brain, eye, and pancreas following ingestion of methyl alcohol and the possible protective role of PPAR-γ modulators. Twenty-four adult Wister albino rats were divided into four groups of six rats each: a control group, a pioglitazone group, a methanol group, and a combined pioglitazone and methanol group. Oxidative stress markers, random blood sugar, insulin, and pancreatic function measurements were evaluated. Western blot analysis for PPAR-γ and Nrf2 protein expressions was performed. Histopathological examination was performed for eye, brain, and pancreas tissues, and the results were compared. PPAR-γ seemed to be incorporated in the development of organ toxicity associated with methyl alcohol ingestion. The protective role of PPAR-γ modulators was achieved through the improvement of assessed pathways. Therefore, damage can be dramatically improved through incorporating PPAR-γ agonists in the management plan of methyl alcohol toxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"110 ","pages":"Pages 53-63"},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619441","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":"Toluene, styrene and methyl-ethyl-ketone inhalation: Effects on the power of cortical oscillations in rats","authors":"E. Bernal Meléndez ,&nbsp;T. Venet ,&nbsp;A. Thomas ,&nbsp;S. Boucard ,&nbsp;L. Guenot ,&nbsp;L. Merlen ,&nbsp;S. Grossmann ,&nbsp;E. Joubert ,&nbsp;M. Mascherin ,&nbsp;S. Viton ,&nbsp;L. Wathier ,&nbsp;F. Cosnier ,&nbsp;B. Pouyatos","doi":"10.1016/j.neuro.2025.07.001","DOIUrl":"10.1016/j.neuro.2025.07.001","url":null,"abstract":"<div><div>Exposure to volatile organic solvents, in both industrial workers and animal models, has a depressant effect on the central nervous system and alters behavior. However, the specific impact on brain activity during acute exposure has not been extensively studied. Here, we assessed how acute exposure to three common industrial solvents - toluene, styrene and methyl-ethyl-ketone (MEK) - affected the power of brain oscillations in rats. Rats (n = 14/group) were implanted with cortical electrodes which were connected to a removable headstage during exposure, to wirelessly transmit digitized electrocorticographic (ECoG) signals. Signals were continuously recorded while the rats inhaled solvent vapors (1000 ppm) for 6 h, with a 1-h control period before and after (breathing filtered air). Experiments were repeated for four successive days. In addition to brain oscillations, post-rotatory nystagmus (PRN) and sensory-motor coordination were tested following air/solvent exposure. MEK had no significant effects on the parameters tested. Styrene decreased the power of overall brain activity, but had no effect on motor activity. Toluene increased the power of fast oscillations (30–90 Hz) within minutes and further over time; concomitantly, the power of slow waves (2–12 Hz) decreased. Motor activity was slightly increased by toluene. Both toluene and styrene increased the number and duration of saccades measured by PRN. Dose-response experiments with styrene (n = 16 rats) revealed significant changes in oscillation power even at 50 ppm. These findings suggest that ECoG can be used to assess solvent effects on brain activity in real-time, surpassing the sensitivity of traditional sensorimotor tests.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"110 ","pages":"Pages 31-41"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605952","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":"Impact of early adolescent lead exposure on brain function and response: Findings from a Chinese cohort","authors":"Olivia M. Halabicky ,&nbsp;Naixue Cui ,&nbsp;Jianghong Liu","doi":"10.1016/j.neuro.2025.06.007","DOIUrl":"10.1016/j.neuro.2025.06.007","url":null,"abstract":"<div><h3>Purpose</h3><div>While the detrimental effects of lead exposure on cognition have been well documented, less research has focused on pre-adolescent populations. The purpose of this study was to understand the relationship between adolescent lead exposure and measures of brain functionality.</div></div><div><h3>Methods</h3><div>In a Chinese early adolescent cohort (N = 258 (50.1 % female) mean age 11.51 years) we examined associations between blood lead levels (BLLs) and P300 event-related potential elicited by three types of stimuli during an auditory oddball task.</div></div><div><h3>Results</h3><div>Mean BLLs in adolescence were 3.17 mcg/dl. In ANOVAs comparing BLL groups above and below the mean, those with greater BLLs had significantly prolonged novelty P300 latency (F=4.67; p = 0.032). In linear models adjusted for age, sex, BLLs at 3–5 years, child IQ, residence location, parent's education, and father’s smoking during pregnancy, increasing BLLs were associated with a 20.21 ms increase in target latency (95 % CI 3.73, 36.69). In sex stratified analyses, a 1 mcg/dl increase in BLLs was associated with a 26.64 ms increase in novel latency in males only (95 % CI 3.49, 49.78).</div></div><div><h3>Discussion</h3><div>Our results suggest a modest association between early adolescent lead exposure and detriments in neurophysiology, particularly related to novelty P300 in males and target P300 in the overall sample. Future research can consider how P300 alterations influence child and adolescent developmental trajectories and test ERP measures as a mediator between early life environmental exposures and later health decision making.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"110 ","pages":"Pages 23-30"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597418","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":"Cannabidiol potentiates phenobarbital-induced cell death in the developing brain","authors":"Rubia Aparecida Fernandes ,&nbsp;João Vitor Melo Ribeiro ,&nbsp;Rodrigo Espindula Torres ,&nbsp;Giovanna Bruno Borges ,&nbsp;Larissa Gabrielly Ribeiro de Freitas ,&nbsp;Olagide Wagner de Castro ,&nbsp;Marcio Flávio Dutra Moraes ,&nbsp;Norberto Garcia-Cairasco ,&nbsp;Fabrício A. Moreira ,&nbsp;Victor Rodrigues Santos","doi":"10.1016/j.neuro.2025.06.005","DOIUrl":"10.1016/j.neuro.2025.06.005","url":null,"abstract":"<div><div>Epilepsy, affecting about 1 % of the global population, is more prevalent in children. The primary treatment is antiseizure medications (ASMs), with phenobarbital (PB) being the most common for pediatric cases. However, PB is effective in only two-thirds of patients and can cause side effects like cell death in developing brains. Early-life epilepsy treatment is particularly challenging, as many patients continue to experience poorly controlled seizures. Due to the limitations of current ASMs, cannabidiol (CBD) has emerged as a promising alternative, offering fewer side effects, neuroprotective properties, and efficacy in treatment-resistant cases. However, its impact on the developing brain remains unclear. In this study, we evaluated the safety profile of CBD in immature rodent brains, with particular attention to possible neurodegenerative effects as detected by Fluoro-Jade C histochemical staining (a sensitive marker of neuronal degeneration. CBD was administered at doses of 2, 20, and 200 mg/kg to postnatal day 7 wistar rats (male and female), with neuronal cell death assessed 24 h later. Results showed no overall increase in cell death compared to controls, suggesting comparable cell viability across doses. Notably, combining CBD 30 mg/kg with PB 75 mg/kg significantly increased neuronal death, with the PB+CBD group showing over twice the neurodegeneration of PB alone. These findings indicate that CBD may exacerbate PB-induced neurotoxicity, countering its expected neuroprotective benefits at certain doses. This highlights the need for caution when combining CBD with PB in pediatric epilepsy treatment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"110 ","pages":"Pages 10-22"},"PeriodicalIF":3.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587407","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":"Iron species in cerebrospinal fluid and dementia risk in subjects with mild cognitive impairment: A cohort study","authors":"Teresa Urbano ,&nbsp;Bernhard Michalke ,&nbsp;Annalisa Chiari ,&nbsp;Carlotta Malagoli ,&nbsp;Roberta Bedin ,&nbsp;Manuela Tondelli ,&nbsp;Marco Vinceti ,&nbsp;Tommaso Filippini","doi":"10.1016/j.neuro.2025.06.006","DOIUrl":"10.1016/j.neuro.2025.06.006","url":null,"abstract":"<div><h3>Background</h3><div>Iron dysregulation has been implicated in the pathogenesis of dementia, since it is an essential nutrient for neuronal function, but also contributes to oxidative stress and neurotoxicity at elevated levels.</div></div><div><h3>Methods</h3><div>We enrolled 56 individuals with newly-diagnosed mild cognitive impairment (MCI) and followed over a 47-month period to monitor conversion to dementia according to baseline percentage concentrations of cerebrospinal fluid iron species.</div></div><div><h3>Results</h3><div>In this cohort, 28 participants developed Alzheimer’s dementia, 5 frontotemporal dementia, 2 Lewy body dementia, and 2 vascular dementia during the follow-up. Higher Fe-Ferritin was associated with a higher though statistically unstable dementia risk (hazard ratio-HR 1.36 for 10-unit % increase, 95 % confidence interval-CI 0.88–2.11), while Fe-Transferrin was linked to a lower risk (HR 0.65, 95 % CI 0.21–2.08) and inorganic Fe showed little association (HR 1.06, 95 % CI 0.80–1.40). Patterns of association were non-linear: inorganic Fe had a U-shaped association, with reduced risk at 25–40 % and increased risk above 45 %; Fe-Ferritin showed an inverted U-shaped relation with higher risk between 10 % and 20 %; Fe-Transferrin showed almost no relation with dementia risk. When considering conversion to Alzheimer’s dementia only, the relation was similarly U-shaped for inorganic Fe and almost null for Fe-Transferrin, while Fe-Ferritin showed a positive relation with risk above 15 %.</div></div><div><h3>Conclusions</h3><div>Despite the statistical imprecision of the estimates, our study provides novel evidence linking iron species in cerebrospinal fluid to dementia risk in individuals with MCI. These findings also underscore the importance of elemental speciation in dementia research.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"110 ","pages":"Pages 1-9"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548594","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":"Mechanisms of micro- and nanoplastics on blood-brain barrier crossing and neurotoxicity: Current evidence and future perspectives","authors":"Yu Ma,&nbsp;Haitao Yang,&nbsp;Shuyan Niu,&nbsp;Menghao Guo,&nbsp;Yuying Xue","doi":"10.1016/j.neuro.2025.06.003","DOIUrl":"10.1016/j.neuro.2025.06.003","url":null,"abstract":"<div><div>Micro- and nanoplastics (MNPs), as emerging global pollutants, pose increasing threats to ecological environments and human health due to their widespread distribution and potential toxicity. Recent studies have demonstrated that MNPs not only enter the human body through multiple pathways but may also cross the blood-brain barrier (BBB), causing irreversible toxic damage to the central nervous system (CNS). This review summarizes the possible mechanisms of MNPs crossing the BBB, including the disruption of tight junctions and adherens juctions, paracellular transport, and endocytosis pathways. We focused on investigating the key roles of oxidative stress, inflammatory responses, mitochondrial dysfunction, and iron metabolism disorders in MNP-induced neurotoxicity, and discovered significant interconnections among these mechanisms. Furthermore, as carriers of pollutants, MNPs can facilitate co-exposure with other environmental contaminants such as heavy metals and persistent organic pollutants, producing synergistic toxic effects that further aggravate neurological damage. This review synthesizes the main research progress in this field, evaluates the potential toxicological impacts of MNPs on the CNS, and identifies key scientific questions that need to be addressed in future research, thereby providing theoretical foundations for in-depth studies of MNP neurotoxicity mechanisms and risk assessment.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 92-107"},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330670","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":"Simultaneous study of cochleotoxicity and vestibulotoxicity of 3,3’- iminodipropionitrile in rats through several experimental approaches","authors":"M. Chalansonnet ,&nbsp;A. Thomas ,&nbsp;S. Boucard ,&nbsp;L. Merlen ,&nbsp;L. Guenot ,&nbsp;T. Venet ,&nbsp;E. Bernal ,&nbsp;B. Pouyatos","doi":"10.1016/j.neuro.2025.06.004","DOIUrl":"10.1016/j.neuro.2025.06.004","url":null,"abstract":"<div><div>Many industrial chemicals and clinical compounds are toxic to the inner ear. Some preferentially target the cochlea or vestibular structures, whereas others are harmful to both. The reasons behind these distinct ototoxic profiles remain poorly understood. The lack of a clear structure-toxicity relationship means that the prediction of the ototoxic potential of new drugs or chemical compounds is challenging and that <em>in vivo</em> testing is necessary. Vestibular or cochlear toxicity can be readily assessed independently, but we lack a method to simultaneously evaluate both functional and histological impairments in the same animals. Here, we describe and test such a method using 3,3’-iminodipropionitrile (IDPN), a compound known to induce hair cell loss in both cochlear and vestibular epithelia in the inner ear of rodents. Female Long-Evans rats were treated with IDPN (0, 150, 200, or 300 mg/kg/day for three days, i.p.). Auditory function was assessed using distortion product otoacoustic emissions (DPOAEs), while vestibular function was evaluated by measuring post-rotatory nystagmus (PRN) and anti-gravity reflexes: the tail-lift and air-righting tests. These tests were conducted before, and four weeks after treatment. Inner ears were collected to count hair cells and to examine the cochlea, utricle, saccule, and cristae by scanning electron microscopy (SEM). Auditory and balance deficits, as well as histological damage in all epithelia, were observed from 200 mg/kg/day, with a strong correlation between functional impairments and histological findings. The method described provides a comprehensive and unbiased means to compare vestibular and cochlear toxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 108-118"},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336763","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":"Protective role of root-derived betulinic acid from Artocarpus heterophyllus against arsenic-induced neurotoxicity in Drosophila melanogaster","authors":"B. Srihari ,&nbsp;K.V. Harish Prashanth","doi":"10.1016/j.neuro.2025.06.002","DOIUrl":"10.1016/j.neuro.2025.06.002","url":null,"abstract":"<div><div>Exposure to arsenic (<strong>As</strong>) has several adverse health effects, including cognitive deficits in humans and animals. In the present study, neuroprotective effect of <em>Artocarpus heterophyllus</em> root derived purified (98 %) betulinic acid powder (BAP) was examined against <strong>As</strong> induced neurotoxicity in <em>Drosophila melanogaster</em> (Oregon K, wild type). BAP was well characterized using HPTLC and LC-MS. Adult flies treated with <strong>As</strong> alone showed significant behaviour deficits, enhanced oxidative stress, neurotoxicity, and mortality. Further, flies were co-fed with BAP along with <strong>As</strong> (0.5 mM) for 7 days. As a result, BAP decreased the mortality rate in a concentration dependent manner against <strong>As</strong> toxicity (36–77 %). Behavioural studies indicated that flies treated with BAP had an improved locomotor phenotype and increased survival potential (18 days) for <strong>As</strong> induced flies. The biochemical analysis revealed that BAP restored <strong>As</strong> induced elevation of oxidative markers in both head and body regions of flies. BAP enhanced the activity of membrane-bound enzymes such as succinate dehydrogenase and NADH-cytochrome c reductase. Additionally, it was found that BAP alleviated cholinergic disturbances and dopamine depletion, which are associated with <strong>As</strong> and bring down abnormal brain architecture to normal. Overall, data suggests that BAP may provide neuromodulatory effects against <strong>As</strong>-induced neurotoxicity by suppressing oxidative stress and attenuating mitochondrial dysfunction.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"109 ","pages":"Pages 80-91"},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}