Neurotoxicology最新文献

{"title":"The synthetic cathinones MDPHP and MDPV: Comparison of the acute effects in mice, in silico ADMET profiles and clinical reports","authors":"Marta Bassi ,&nbsp;Sabrine Bilel ,&nbsp;Micaela Tirri ,&nbsp;Giorgia Corli ,&nbsp;Fabiana Di Rosa ,&nbsp;Adolfo Gregori ,&nbsp;Alaaldin M. Alkilany ,&nbsp;Ousama Rachid ,&nbsp;Elisa Roda ,&nbsp;Fabrizio De Luca ,&nbsp;Pietro Papa ,&nbsp;Eleonora Buscaglia ,&nbsp;Giorgio Zauli ,&nbsp;Carlo Alessandro Locatelli ,&nbsp;Matteo Marti","doi":"10.1016/j.neuro.2024.06.014","DOIUrl":"10.1016/j.neuro.2024.06.014","url":null,"abstract":"<div><p>The 3,4-methylenedioxy-alpha-pyrrolidinohexanophenone (MDPHP) is a synthetic cathinone closely related to 3,4-methylenedioxypyrovalerone (MDPV), one of the most common synthetic cathinones present in the “bath salts”. MDPHP has recently gained attention due to increasing seizures and involvement in human intoxications which occurred in Europe and Italy in the last years, but currently there is a lack of information about its pharmaco-toxicological effects. With the aim at filling this gap, the present study is endeavoured to (i) evaluate the effects of acute administration of MDPHP (0.01–20 mg/kg; i.p.) on behaviour, cardiorespiratory and cardiovascular parameters in CD-1 male mice, comparing them to those observed after administration of MDPV; (ii) predict the ADMET profile of the two analogues using the Plus ADMET Predictor®; (iii) present clinical data related to MDPHP and MDPV-induced intoxications recorded between 2011 and 2023 by the Pavia Poison Control Centre (PCC) − National Toxicology Information Centre (Istituti Clinici Scientifici Maugeri, IRCCS Pavia, Italy). Our results substantiated that MDPHP and MDPV similarly affect sensorimotor and behavioural responses in mice, importantly increased locomotion and induced aggressive behaviour, and, at higher dosage, increased heart rate and blood pressure. These findings are in line with those observed in humans, revealing severe toxidromes typically characterized by Central Nervous System (CNS) alterations (behavioural/neuropsychiatric symptoms), including psychomotor agitation and aggressiveness, cardiovascular and respiratory disorders (e.g. tachycardia, hypertension, dyspnoea), and other peripheral symptoms (e.g. hyperthermia, acidosis, rhabdomyolysis).</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 230-255"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161813X2400069X/pdfft?md5=f4ef8f3f20138252da308e0c9e6ae45a&pid=1-s2.0-S0161813X2400069X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492767","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}

{"title":"Cannabis use in Parkinson’s disease: Patient access to medical cannabis and physician perspective on product safety","authors":"Symone T. Griffith ,&nbsp;Kendra D. Conrow ,&nbsp;Michael Go ,&nbsp;Mindy L. McEntee ,&nbsp;Raminta Daniulaityte ,&nbsp;Majia H. Nadesan ,&nbsp;Mathew R. Swinburne ,&nbsp;Holly A. Shill ,&nbsp;Maxwell C.K. Leung","doi":"10.1016/j.neuro.2024.05.008","DOIUrl":"10.1016/j.neuro.2024.05.008","url":null,"abstract":"<div><p>The rate of medical cannabis use has increased in parallel with the number of states legalizing its use. Parkinson’s disease (PD) patients are of particular concern due to their higher cannabis use rate than in the general US population (25–40 % PD patient cannabis users vs. ∼18 % in the general population), as well as their susceptibility to environmental contaminants in cannabis, including pesticides, toxic elements, solvents, microbes, and mycotoxins. In order to address the complex nature of this industry, we examined the changes in PD-related qualifying conditions in the U.S. from 2019 to 2023. We also conducted an online survey to gain insight into the knowledge, risk perceptions, and opinions regarding medical cannabis and contamination issues from physicians who treated PD patients. The number of states including PD-related qualifying conditions increased over the past 5 years from 28 to 36 states. These conditions included PD (increasing from 14 to 16 states), muscle spasms (14 to 24), anxiety (1 to 5), and pain (17 to 35). State-by-state comparisons revealed high variability in the language used to describe the different qualifying conditions. Online surveys were sent out to 45 neurologists and movement disorder specialists who primarily treated PD patients. The response rate was 44 % from nine states (AZ, CA, FL, MA, MN, WI, PA, IL, and NM). When asked if they were aware of any contaminants in cannabis products, we found that 65 % of the physicians were unaware of any contaminants commonly found in cannabis and only 25 %, 15 %, and 15 % of them were aware of pesticide, toxic element, and solvent contaminants, respectively. In their free-text opinion response on the health impact of cannabis-borne contaminants, “long-term effect” (35 %) and “comorbidities and PD prognosis” (40 %) were identified as the two most common themes. These results point to the need for further regulatory deliberation regarding risks and susceptibility to cannabis contaminants. Additionally, education is needed to inform physicians on cannabis safety issues. Further research will identify the implementation strategies to reduce contaminant exposure and protect patient health.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 198-205"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161813X24000536/pdfft?md5=11b9f99a233c5d88df0490b7031301c5&pid=1-s2.0-S0161813X24000536-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248385","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}

{"title":"Impaired memory in Sprague-Dawley rats exposed to complex groundwater mixtures of contaminants is associated with reduced cranial blood flow and hippocampal neurotoxicity","authors":"B. Boamah ,&nbsp;C. Morse ,&nbsp;S. Siciliano ,&nbsp;N. Hogan ,&nbsp;M. Hecker ,&nbsp;M. Hanson ,&nbsp;P. Campbell ,&nbsp;R. Peters ,&nbsp;A.N. Al-Dissi ,&nbsp;T.D. Olver ,&nbsp;L. Weber","doi":"10.1016/j.neuro.2024.07.005","DOIUrl":"10.1016/j.neuro.2024.07.005","url":null,"abstract":"<div><p>Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10 % v/v low impact groundwater, and (iii) 0.01 %, 0.1 %, 1 %, and 10 % high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 288-296"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161813X24000779/pdfft?md5=4a9bcdd78d97ba2f51f8d02c65aba687&pid=1-s2.0-S0161813X24000779-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590927","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}

{"title":"Identification of neural-relevant toxcast high-throughput assay intended gene targets: Applicability to neurotoxicity and neurotoxicant putative molecular initiating events","authors":"Cina M. Mack ,&nbsp;Alethea Tsui-Bowen ,&nbsp;Alicia R. Smith ,&nbsp;Karl F. Jensen ,&nbsp;Prasada Rao S. Kodavanti ,&nbsp;Virginia C. Moser ,&nbsp;William R. Mundy ,&nbsp;Timothy J. Shafer ,&nbsp;David W. Herr","doi":"10.1016/j.neuro.2024.07.001","DOIUrl":"10.1016/j.neuro.2024.07.001","url":null,"abstract":"<div><p>The US EPA’s Toxicity Forecaster (ToxCast) is a suite of high-throughput <em>in vitro</em> assays to screen environmental toxicants and predict potential toxicity of uncharacterized chemicals. This work examines the relevance of ToxCast assay intended gene targets to putative molecular initiating events (MIEs) of neurotoxicants. This effort is needed as there is growing interest in the regulatory and scientific communities about developing new approach methodologies (NAMs) to screen large numbers of chemicals for neurotoxicity and developmental neurotoxicity. Assay gene function (GeneCards, NCBI-PUBMED) was used to categorize gene target neural relevance (1 = neural, 2 = neural development, 3 = general cellular process, 3 A = cellular process critical during neural development, 4 = unlikely significance). Of 481 unique gene targets, 80 = category 1 (16.6 %); 16 = category 2 (3.3 %); 303 = category 3 (63.0 %); 97 = category 3 A (20.2 %); 82 = category 4 (17.0 %). A representative list of neurotoxicants (548) was researched (ex. PUBMED, PubChem) for neurotoxicity associated MIEs/Key Events (KEs). MIEs were identified for 375 compounds, whereas only KEs for 173. ToxCast gene targets associated with MIEs were primarily neurotransmitter (ex. dopaminergic, GABA)receptors and ion channels (calcium, sodium, potassium). Conversely, numerous MIEs associated with neurotoxicity were absent. Oxidative stress (OS) mechanisms were 79.1 % of KEs. In summary, 40 % of ToxCast assay gene targets are relevant to neurotoxicity mechanisms. Additional receptor and ion channel subtypes and increased OS pathway coverage are identified for potential future assay inclusion to provide more complete coverage of neural and developmental neural targets in assessing neurotoxicity.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 256-265"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559337","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":"Luteolin protects mouse hippocampal neuronal cells against isoflurane-induced neurotoxicity through miR-214/PTEN/Akt pathway","authors":"Guodong Zhang ,&nbsp;Chuang Sun ,&nbsp;Gang Zhou ,&nbsp;Qihang Zhang","doi":"10.1016/j.neuro.2024.07.008","DOIUrl":"10.1016/j.neuro.2024.07.008","url":null,"abstract":"<div><p>Isoflurane is one of the most commonly used anaesthetic agents in surgery procedures. During the past decades, isoflurane has been found to cause impairment in neurological capabilities in new-borns and elderly patients. Luteolin is a flavonoid that has been documented to possess a neuroprotective effect. Here we investigated the putative neuroprotective effects of luteolin on isoflurane-induced neurotoxicity in mouse hippocampal neuronal HT22 cells and explored the potential mechanisms. We demonstrated that luteolin improved mitochondrial dysfunction and reduced oxidative stress and apoptosis in isoflurane-treated HT22 cells, and thus inhibiting the isoflurane-induced neuronal injury. Further investigations showed that isoflurane exposure caused miR-214 downregulation, which could be mitigated by treatment with luteolin. Knockdown of miR-214 attenuated the neuroprotection of luteolin on isoflurane-induced neuronal injury. More importantly, luteolin inhibited isoflurane-caused regulation of the PTEN/Akt pathway, while miR-214 knockdown altered the regulatory effect of luteolin on the PTEN/Akt pathway. Furthermore, the effects of miR-214 knockdown on the neuroprotection of luteolin could also be prevented by knockdown of PTEN, implying that the neuroprotective effect of luteolin was mediated by miR-214/PTEN/Akt signaling pathway. These findings provided evidence for the potential application of luteolin in preventing isoflurane-induced neurotoxicity.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 310-319"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616897","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":"STIM1 mediates methamphetamine-induced neuronal autophagy and apoptosis","authors":"Qin Tian ,&nbsp;Jie Zhou ,&nbsp;Zhenzhen Xu ,&nbsp;Bin Wang ,&nbsp;Jiashun Liao ,&nbsp;Ke Duan ,&nbsp;Xiaoting Li ,&nbsp;Enping Huang ,&nbsp;Wei-Bing Xie","doi":"10.1016/j.neuro.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.neuro.2024.06.006","url":null,"abstract":"<div><p>Methamphetamine (METH) is a widely abused amphetamine-type psychoactive drug that causes serious health problems. Previous studies have demonstrated that METH can induce neuron autophagy and apoptosis in vivo and in vitro. However, the molecular mechanisms underlying METH-induced neuron autophagy and apoptosis remain poorly understood. Stromal interacting molecule 1 (STIM1) was hypothesized to be involved in METH-induced neuron autophagy and apoptosis. Therefore, the expression of STIM1 protein was measured and the effect of blocking STIM1 expression with siRNA was investigated in cultured neuronal cells, and the hippocampus and striatum of mice exposed to METH. Furthermore, intracellular calcium concentration and endoplasmic reticulum (ER) stress-related proteins were determined in vitro and in vivo in cells treated with METH. The results suggested that STIM1 mediates METH-induced neuron autophagy by activating the p-Akt/p-mTOR pathway. METH exposure also resulted in increased expression of Orai1, which was reversed after STIM1 silencing. Moreover, the disruption of intracellular calcium homeostasis induced ER stress and up-regulated the expression of pro-apoptotic protein CCAAT/enhancer-binding protein homologous protein (CHOP), resulting in classic mitochondria apoptosis. METH exposure can cause neuronal autophagy and apoptosis by increasing the expression of STIM1 protein; thus, STIM1 may be a potential gene target for therapeutics in METH-caused neurotoxicity.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 134-145"},"PeriodicalIF":3.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429482","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 the Fox River PCB mixture modulates behavior in juvenile mice","authors":"Rebecca J. Wilson ,&nbsp;Youjun P. Suh ,&nbsp;Ilknur Dursun ,&nbsp;Xueshu Li ,&nbsp;Felipe da Costa Souza ,&nbsp;Ana Cristina Grodzki ,&nbsp;Julia Y. Cui ,&nbsp;Hans-Joachim Lehmler ,&nbsp;Pamela J. Lein","doi":"10.1016/j.neuro.2024.06.008","DOIUrl":"10.1016/j.neuro.2024.06.008","url":null,"abstract":"<div><p>Developmental exposures to PCBs are implicated in the etiology of neurodevelopmental disorders (NDDs). This observation is concerning given the continued presence of PCBs in the human environment and the increasing incidence of NDDs. Previous studies reported that developmental exposure to legacy commercial PCB mixtures (Aroclors) or single PCB congeners found in Aroclors caused NDD-relevant behavioral phenotypes in animal models. However, the PCB congener profile in contemporary human samples is dissimilar to that of the legacy Aroclors, raising the question of whether human-relevant PCB mixtures similarly interfere with normal brain development. To address this question, we assessed the developmental neurotoxicity of the Fox River Mixture (FRM), which was designed to mimic the congener profile identified in fish from the PCB-contaminated Fox River that constitute a primary protein source in the diet of surrounding communities. Adult female C57BL/6 J mouse dams (8–10 weeks old) were exposed to vehicle (peanut oil) or FRM at 0.1, 1.0, or 6.0 mg/kg/d in their diet throughout gestation and lactation, and neurodevelopmental outcomes were assessed in their pups. Ultrasonic vocalizations (USVs) and measures of general development were quantified at postnatal day (P) 7, while performance in the spontaneous alternation task and the 3-chambered social approach/social novelty task was assessed on P35. Triiodothyronine (T3) and thyroxine (T4) were quantified in serum collected from the dams when pups were weaned and from pups on P28 and P35. Developmental exposure to FRM did not alter pup weight or body temperature on P7, but USVs were significantly decreased in litters exposed to FRM at 0.1 or 6.0 mg/kg/d in the maternal diet. FRM also impaired male and female pups’ performance in the social novelty task. Compared to sex-matched vehicles, significantly decreased social novelty was observed in male and female pups in the 0.1 and 6.0 mg/kg/d dose groups. FRM did not alter performance in the spontaneous alternation or social approach tasks. FRM increased serum T3 levels but decreased serum T4 levels in P28 male pups in the 1.0 and 6.0 mg/kg/d dose groups. In P35 female pups and dams, serum T3 levels decreased in the 6.0 mg/kg/d dose group while T4 levels were not altered. Collectively, these findings suggest that FRM interferes with the development of social communication and social novelty, but not memory, supporting the hypothesis that contemporary PCB exposures pose a risk to the developing brain. FRM had sex, age, and dose-dependent effects on serum thyroid hormone levels that overlapped but did not perfectly align with the FRM effects on behavioral outcomes. These observations suggest that changes in thyroid hormone levels are not likely the major factor underlying the behavioral deficits observed in FRM-exposed animals.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 146-161"},"PeriodicalIF":3.4,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161813X24000627/pdfft?md5=5e1e82999e6b042df55e51fcbe90ae40&pid=1-s2.0-S0161813X24000627-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141406041","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}

{"title":"Brain gray matter volume of reward-related structures in Inuit adolescents pre- and postnatally exposed to lead, mercury and polychlorinated biphenyls","authors":"Avril Gagnon-Chauvin ,&nbsp;Mathieu Fornasier-Bélanger ,&nbsp;Sandra W. Jacobson ,&nbsp;Joseph L. Jacobson ,&nbsp;Yohann Courtemanche ,&nbsp;Pierre Ayotte ,&nbsp;Richard E. Bélanger ,&nbsp;Gina Muckle ,&nbsp;Dave Saint-Amour","doi":"10.1016/j.neuro.2024.06.009","DOIUrl":"10.1016/j.neuro.2024.06.009","url":null,"abstract":"<div><p>This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of key regions of the brain reward circuit, namely the caudate nucleus, putamen, nucleus accumbens (nAcc), the amygdala, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). Structural magnetic resonance imaging (MRI) was conducted in 77 Inuit adolescents (mean age = 18.39) from Nunavik, Canada, who also completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking – 2 (SS-2), two self-report questionnaires evaluating the tendency toward sensation seeking, which is a proxy of reward-related behaviors. Exposures to Pb, Hg and PCBs were measured in cord blood at birth, in blood samples at 11 years old and at time of testing (18 years old). Multivariate linear regressions were corrected for multiple comparisons and adjusted for potential confounders, such as participants’ sociodemographic characteristics and nutrient fish intake. Results showed that higher cord blood Pb levels predicted smaller gray matter volume in the bilateral nAcc, caudate nucleus, amygdala and OFC as well as in left ACC. A moderating effect of sex was identified, indicating that the Pb-related reduction in volume in the nAcc and caudate nucleus was more pronounced in female. Higher blood Hg levels at age 11 predicted smaller right amygdala independently of sex. No significant associations were found between blood PCBs levels at all three times of exposure. This study provides scientific support for the detrimental effects of prenatal Pb and childhood Hg blood concentrations on gray matter volume in key reward-related brain structures.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 162-174"},"PeriodicalIF":3.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161813X24000640/pdfft?md5=d575ad207560274b80e50ff0534d9357&pid=1-s2.0-S0161813X24000640-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331500","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}

{"title":"The effect of graphene oxide administration on the brains of male mice: Behavioral study and assessment of oxidative stress","authors":"Asmaa Rhazouani ,&nbsp;Halima Gamrani ,&nbsp;Lhoucine Gebrati ,&nbsp;Tonni Agustiono Kurniawan ,&nbsp;Faissal Aziz","doi":"10.1016/j.neuro.2024.06.010","DOIUrl":"10.1016/j.neuro.2024.06.010","url":null,"abstract":"<div><p>Graphene oxide (GO) nanoparticles are attracting growing interest in various fields, not least because of their distinct characteristics and possible uses. However, concerns about their impact on neurological health are emerging, underlining the need for in-depth studies to assess their neurotoxicity. This study examines GO exposure's neurobehavioral and biochemical effects on the central nervous system (CNS). To this end, we administered two doses of GO (2 and 5 mg/kg GO) to mice over a 46-day treatment period. We performed a battery of behavioral tests on the mice, including the open field to assess locomotor activity, the maze plus to measure anxiety, the pole test to assess balance and the rotarod to measure motor coordination. In parallel, we analyzed malondialdehyde (MDA) levels and catalase activity in the brains of mice exposed to GO nanoparticles. In addition, X-ray energy dispersive (EDX) analysis was performed to determine the molecular composition of the brain. Our observations reveal brain alterations in mice exposed to GO by intraperitoneal injection, demonstrating a dose-dependent relationship. We identified behavioral alterations in mice exposed to GO, such as increased anxiety, decreased motor coordination, reduced locomotor activity and balance disorders. These changes were dose-dependent, suggesting a correlation between the amount of GO administered and the extent of behavioral alterations. At the same time, a dose-dependent increase in malondialdehyde and catalase activity was observed, reinforcing the correlation between exposure intensity and associated biochemical responses.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 189-197"},"PeriodicalIF":3.4,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321310","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 pyrethroid exposure in mouse leads to disrupted brain metabolism in adulthood","authors":"Melissa A. Curtis ,&nbsp;Nilanjana Saferin ,&nbsp;Jennifer H. Nguyen ,&nbsp;Ali S. Imami ,&nbsp;William G. Ryan ,&nbsp;Kari L. Neifer ,&nbsp;Gary W. Miller ,&nbsp;James P. Burkett","doi":"10.1016/j.neuro.2024.06.007","DOIUrl":"10.1016/j.neuro.2024.06.007","url":null,"abstract":"<div><p>Environmental and genetic risk factors, and their interactions, contribute significantly to the etiology of neurodevelopmental disorders (NDDs). Recent epidemiology studies have implicated pyrethroid pesticides as an environmental risk factor for autism and developmental delay. Our previous research showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice caused male-biased changes in the brain and in NDD-relevant behaviors in adulthood. Here, we used a metabolomics approach to determine the broadest possible set of metabolic changes in the adult male mouse brain caused by low-dose pyrethroid exposure during development. Using a litter-based design, we exposed mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. We raised male offspring to adulthood and collected whole brain samples for untargeted high-resolution metabolomics analysis. Developmentally exposed mice had disruptions in 116 metabolites which clustered into pathways for folate biosynthesis, retinol metabolism, and tryptophan metabolism. As a cross-validation, we integrated metabolomics and transcriptomics data from the same samples, which confirmed previous findings of altered dopamine signaling. These results suggest that pyrethroid exposure during development leads to disruptions in metabolism in the adult brain, which may inform both prevention and therapeutic strategies.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 87-95"},"PeriodicalIF":3.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321309","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}