Neurotoxicity Research最新文献

{"title":"Cerebral White Matter Alterations Associated With Oligodendrocyte Vulnerability in Organic Acidurias: Insights in Glutaric Aciduria Type I.","authors":"Eugenia Isasi, Moacir Wajner, Juliana Avila Duarte, Silvia Olivera-Bravo","doi":"10.1007/s12640-024-00710-6","DOIUrl":"10.1007/s12640-024-00710-6","url":null,"abstract":"<p><p>The white matter is an important constituent of the central nervous system, containing axons, oligodendrocytes, and its progenitor cells, astrocytes, and microglial cells. Oligodendrocytes are central for myelin synthesis, the insulating envelope that protects axons and allows normal neural conduction. Both, oligodendrocytes and myelin, are highly vulnerable to toxic factors in many neurodevelopmental and neurodegenerative disorders associated with disturbances of myelination. Here we review the main alterations in oligodendrocytes and myelin observed in some organic acidurias/acidemias, which correspond to inherited neurometabolic disorders biochemically characterized by accumulation of potentially neurotoxic organic acids and their derivatives. The yet incompletely understood mechanisms underlying the high vulnerability of OLs and/or myelin in glutaric acidemia type I, the most prototypical cerebral organic aciduria, are particularly discussed.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 4","pages":"33"},"PeriodicalIF":2.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498561","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 Excitotoxicity, Oxidative Stress and Bioenergetics Disruption in the Neuropathology of Nonketotic Hyperglycinemia.","authors":"Guilhian Leipnitz, Jaqueline Santana da Rosa, Moacir Wajner","doi":"10.1007/s12640-024-00711-5","DOIUrl":"10.1007/s12640-024-00711-5","url":null,"abstract":"<p><p>Nonketotic hyperglycinemia (NKH) is an inherited disorder of amino acid metabolism biochemically characterized by the accumulation of glycine (Gly) predominantly in the brain. Affected patients usually manifest with neurological symptoms including hypotonia, seizures, epilepsy, lethargy, and coma, the pathophysiology of which is still not completely understood. Treatment is limited and based on lowering Gly levels aiming to reduce overstimulation of N-methyl-D-aspartate (NMDA) receptors. Mounting in vitro and in vivo animal and human evidence have recently suggested that excitotoxicity, oxidative stress, and bioenergetics disruption induced by Gly are relevant mechanisms involved in the neuropathology of NKH. This brief review gives emphasis to the deleterious effects of Gly in the brain of patients and animal models of NKH that may offer perspectives for the development of novel adjuvant treatments for this disorder.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 4","pages":"32"},"PeriodicalIF":2.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469703","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":"FOXA1 Suppresses Endoplasmic Reticulum Stress, Oxidative Stress, and Neuronal Apoptosis in Parkinson's Disease by Activating PON2 Transcription.","authors":"Jiahui Liu, Yu Fan, Jinyu Chen, Meili Zhao, Changchun Jiang","doi":"10.1007/s12640-024-00709-z","DOIUrl":"10.1007/s12640-024-00709-z","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER) stress and oxidative stress (OS) are often related states in pathological conditions including Parkinson's disease (PD). This study investigates the role of anti-oxidant protein paraoxonase 2 (PON2) in ER stress and OS in PD, along with its regulatory molecule. PD was induced in C57BL/6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment and in SH-SY5Y cells using 1-methyl-4-phenylpyridinium. PON2 was found to be poorly expressed in the substantia nigra pars compacta (SNc) of PD mice, and its overexpression improved motor coordination of mice. Through the evaluation of tyrosine hydroxylase, dopamine transporter, reactive oxygen species (ROS), and C/EBP homologous protein (CHOP) levels and neuronal loss in mice, as well as the examination of CHOP, glucose-regulated protein 94 (GRP94), GRP78, caspase-12, sarco/endoplasmic reticulum calcium ATPase 2, malondialdehyde, and superoxide dismutase levels in SH-SY5Y cells, we observed that PON2 overexpression mitigated ER stress, OS, and neuronal apoptosis both in vivo and in vitro. Forkhead box A1 (FOXA1) was identified as a transcription factor binding to the PON2 promoter to activate its transcription. Upregulation of FOXA1 similarly protected against neuronal loss by alleviating ER stress and OS, while the protective roles were abrogated by additional PON2 silencing. In conclusion, this study demonstrates that FOXA1-mediated transcription of PON2 alleviates ER stress and OS, ultimately reducing neuronal apoptosis in PD.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 4","pages":"31"},"PeriodicalIF":2.9,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458396","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":"PEG300 Protects Mitochondrial Function By Upregulating PGC-1α to Delay Central Nervous System Oxygen Toxicity in Mice.","authors":"Xin Li, Yue Shen, Dan Li, Kun Zhang, Jia Liu, Lu Yao, Jun Yang, Jiao Qian","doi":"10.1007/s12640-024-00708-0","DOIUrl":"10.1007/s12640-024-00708-0","url":null,"abstract":"<p><p>Central nervous system oxygen toxicity (CNS-OT) is a complication of hyperbaric oxygen (HBO) treatment, with limited prevention and treatment options available. In this study, we aimed to explore the effect of polyethylene glycol 300 (PEG300) on CNS-OT and underlying mechanisms. Motor and cognitive functions of mice in normobaric conditions were evaluated by Morris water maze, passive active avoidance, and rotarod tests. HBO was applied at 6 atmospheres absolute (ATA) for 30 min after drug administration. The latency period of convulsion in mice was recorded, and hippocampal tissues were extracted for biochemical experiments. Our experimental results showed that PEG300 extended the convulsion latencies in CNS-OT mice, reduced oxidative stress and inflammation levels in hippocampal tissues. Furthermore, PEG300 preserved mitochondrial integrity and maintained mitochondrial membrane potential in hippocampal tissue by upregulating Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α). This protective effect was enhanced following the administration of ZLN005, an agonist of PGC-1a. Hence, our study suggests that PEG300 might exert protective effects by upregulating PGC-1α expression and preserving mitochondrial health, offering promising prospects for CNS-OT treatment.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 4","pages":"30"},"PeriodicalIF":2.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331504","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":"Assessment of Hippocampal-Related Behavioral Changes in Adolescent Rats of both Sexes Following Voluntary Intermittent Ethanol Intake and Noise Exposure: A Putative Underlying Mechanism and Implementation of a Non-pharmacological Preventive Strategy.","authors":"G E Buján, L D'Alessio, H A Serra, L R Guelman, S J Molina","doi":"10.1007/s12640-024-00707-1","DOIUrl":"10.1007/s12640-024-00707-1","url":null,"abstract":"<p><p>Ethanol (EtOH) intake and noise exposure are particularly concerning among human adolescents because the potential to harm brain. Unfortunately, putative underlying mechanisms remain to be elucidated. Moreover, implementing non-pharmacological strategies, such as enriched environments (EE), would be pertinent in the field of neuroprotection. This study aims to explore possible underlying triggering mechanism of hippocampus-dependent behaviors in adolescent animals of both sexes following ethanol intake, noise exposure, or a combination of both, as well as the impact of EE. Adolescent Wistar rats of both sexes were subjected to an intermittent voluntary EtOH intake paradigm for one week. A subgroup of animals was exposed to white noise for two hours after the last session of EtOH intake. Some animals of both groups were housed in EE cages. Hippocampal-dependent behavioral assessment and hippocampal oxidative state evaluation were performed. Results show that different hippocampal-dependent behavioral alterations might be induced in animals of both sexes after EtOH intake and sequential noise exposure, that in some cases are sex-specific. Moreover, hippocampal oxidative imbalance seems to be one of the potential underlying mechanisms. Additionally, most behavioral and oxidative alterations were prevented by EE. These findings suggest that two frequently found environmental agents may impact behavior and oxidative pathways in both sexes in an animal model. In addition, EE resulted a partially effective neuroprotective strategy. Therefore, it could be suggested that the implementation of a non-pharmacological approach might also potentially provide neuroprotective advantages against other challenges. Finally, considering its potential for translational human benefit might be worth.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 3","pages":"29"},"PeriodicalIF":2.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296483","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":"Rotenone Induces a Neuropathological Phenotype in Cholinergic-like Neurons Resembling Parkinson's Disease Dementia (PDD).","authors":"Daniela Giraldo-Berrio, Miguel Mendivil-Perez, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio","doi":"10.1007/s12640-024-00705-3","DOIUrl":"10.1007/s12640-024-00705-3","url":null,"abstract":"<p><p>Parkinson's disease with dementia (PDD) is a neurological disorder that clinically and neuropathologically overlaps with Parkinson's disease (PD) and Alzheimer's disease (AD). Although it is assumed that alpha-synuclein ( <math><mi>α</mi></math> -Syn), amyloid beta (A <math><mi>β</mi></math> ), and the protein Tau might synergistically induce cholinergic neuronal degeneration, presently the pathological mechanism of PDD remains unclear. Therefore, it is essential to delve into the cellular and molecular aspects of this neurological entity to identify potential targets for prevention and treatment strategies. Cholinergic-like neurons (ChLNs) were exposed to rotenone (ROT, 10 <math><mi>μ</mi></math> M) for 24 h. ROT provokes loss of <math><mrow><mi>Δ</mi> <mrow><mi>Ψ</mi> <mi>m</mi></mrow> </mrow> </math> , generation of reactive oxygen species (ROS), phosphorylation of leucine-rich repeated kinase 2 (LRRK2 at Ser⁹³⁵) concomitantly with phosphorylation of <math><mi>α</mi></math> -synuclein ( <math><mi>α</mi></math> -Syn, Ser¹²⁹), induces accumulation of intracellular A <math><mi>β</mi></math> (iA <math><mi>β</mi></math> ), oxidized DJ-1 (Cys¹⁰⁶), as well as phosphorylation of TAU (Ser²⁰²/Thr²⁰⁵), increases the phosphorylation of c-JUN (Ser⁶³/Ser⁷³), and increases expression of proapoptotic proteins TP53, PUMA, and cleaved caspase 3 (CC3) in ChLNs. These neuropathological features resemble those reproduced in presenilin 1 (PSEN1) E280A ChLNs. Interestingly, anti-oxidant and anti-amyloid cannabidiol (CBD), JNK inhibitor SP600125 (SP), TP53 inhibitor pifithrin- <math><mi>α</mi></math> (PFT), and LRRK2 kinase inhibitor PF-06447475 (PF475) significantly diminish ROT-induced oxidative stress (OS), proteinaceous, and cell death markers in ChLNs compared to naïve ChLNs. In conclusion, ROT induces p- <math><mi>α</mi></math> -Syn, iA <math><mi>β</mi></math> , p-Tau, and cell death in ChLNs, recapitulating the neuropathology findings in PDD. Our report provides an excellent in vitro model to test for potential therapeutic strategies against PDD. Our data suggest that ROT induces a neuropathologic phenotype in ChLNs similar to that caused by the mutation PSEN1 E280A.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 3","pages":"28"},"PeriodicalIF":2.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262426","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":"Fer-1 Protects against Isoflurane-Induced Ferroptosis in Astrocytes and Cognitive Impairment in Neonatal Mice.","authors":"Peng Zhang, Xiaotong Shi, Danyi He, Yu Hu, Yongchao Zhang, Youyi Zhao, Sanxing Ma, Shuhui Cao, Meiting Zhai, Ze Fan","doi":"10.1007/s12640-024-00706-2","DOIUrl":"10.1007/s12640-024-00706-2","url":null,"abstract":"<p><p>Early and prolonged exposure to anesthetic agents could cause neurodevelopmental disorders in children. Astrocytes, heavily outnumber neurons in the brain, are crucial regulators of synaptic formation and function during development. However, how general anesthetics act on astrocytes and the impact on cognition are still unclear. In this study, we investigated the role of ferroptosis and GPX4, a major hydroperoxide scavenger playing a pivotal role in suppressing the process of ferroptosis, and their underlying mechanism in isoflurane-induced cytotoxicity in astrocytes and cognitive impairment. Our results showed that early 6 h isoflurane anesthesia induced cognitive impairment in mice. Ferroptosis-relative genes and metabolic changes were involved in the pathological process of isoflurane-induced cytotoxicity in astrocytes. The level of GPX4 was decreased while the expression of 4-HNE and generation of ROS were elevated after isoflurane exposure. Selectively blocking ferroptosis with Fer-1 attenuated the abovementioned cytotoxicity in astrocytes, paralleling with the reverse of the changes in GPX4, ROS and 4-HNE secondary to isoflurane anesthesia. Fer-1 attenuated the cognitive impairment induced by prolonged isoflurane exposure. Thus, ferroptosis conduced towards isoflurane-induced cytotoxicity in astrocytes via suppressing GPX4 and promoting lipid peroxidation. Fer-1 was expected to be an underlying intervention for the neurotoxicity induced by isoflurane in the developing brain, and to alleviate cognitive impairment in neonates.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 3","pages":"27"},"PeriodicalIF":2.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180237","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":"Correction to: Connexin 43 Promotes Neurogenesis via Regulating Aquaporin-4 after Cerebral Ischemia.","authors":"Heling Chu, Jing Dong, Yuping Tang, Chuyi Huang, Qihao Guo","doi":"10.1007/s12640-024-00701-7","DOIUrl":"10.1007/s12640-024-00701-7","url":null,"abstract":"","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 3","pages":"26"},"PeriodicalIF":2.9,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869823","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":"Hyperoxia and brain: the link between necessity and injury from a molecular perspective","authors":"Richard Simon Machado, Khiany Mathias, Larissa Joaquim, Rafaella Willig de Quadros, Gislaine Tezza Rezin, Fabricia Petronilho","doi":"10.1007/s12640-024-00702-6","DOIUrl":"https://doi.org/10.1007/s12640-024-00702-6","url":null,"abstract":"<p>Oxygen (O₂) supplementation is commonly used to treat hypoxia in patients with respiratory failure. However, indiscriminate use can lead to hyperoxia, a condition detrimental to living tissues, particularly the brain. The brain is sensitive to reactive oxygen species (ROS) and inflammation caused by high concentrations of O₂, which can result in brain damage and mitochondrial dysfunction, common features of neurodegenerative disorders. Hyperoxia leads to increased production of ROS, causing oxidative stress, an imbalance between oxidants and antioxidants, which can damage tissues. The brain is particularly vulnerable to oxidative stress due to its lipid composition, high O₂ consumption rate, and low levels of antioxidant enzymes. Moreover, hyperoxia can cause vasoconstriction and decreased O₂ supply to the brain, posing a challenge to redox balance and neurodegenerative processes. Studies have shown that the severity of hyperoxia-induced brain damage varies with inspired O₂ concentration and duration of exposure. Therefore, careful evaluation of the balance between benefits and risks of O₂ supplementation, especially in clinical settings, is crucial.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"94 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598751","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":"Melatonin is a Neuroprotective and Antioxidant Agent against Neurotoxicity Induced by an Intrahippocampal Injection of Nickel in Rats","authors":"Mohamed Yassine El Brouzi, Mouloud Lamtai, Oussama Zghari, Abdelghafour El Hamzaoui, Ayoub Rezqaoui, Zahra Hadch, Nada Fath, Ali Ouichou, Aboubaker El Hessni, Abdelhalem Mesfioui","doi":"10.1007/s12640-024-00700-8","DOIUrl":"https://doi.org/10.1007/s12640-024-00700-8","url":null,"abstract":"<p>The investigation into the hippocampal function and its response to heavy metal exposure is crucial for understanding the mechanisms underlying neurotoxicity, this can potentially inform strategies for mitigating the adverse effects associated with heavy metal exposure. Melatonin is an essential neuromodulator known for its efficacy as an antioxidant. In this study, we aimed to determine whether melatonin could protect against Nickel (Ni) neurotoxicity. To achieve this, we performed an intracerebral injection of Ni (300 µM NiCl₂) into the right hippocampus of male Wistar rats, followed by melatonin treatment. Based on neurobehavioral and neurobiochemical assessments, our results demonstrate that melatonin efficiently enhances Ni-induced behavioral dysfunction and cognitive impairment. Specifically, melatonin treatment positively influences anxious behavior, significantly reduces immobility time in the forced swim test (FST), and improves learning and spatial memory abilities. Moreover, neurobiochemical assays revealed that melatonin treatment modulates the Ni-induced alterations in oxidative stress balance by increasing antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase (CAT). Additionally, we observed that melatonin significantly attenuated the increased levels of lipid peroxidation (LPO) and nitric oxide (NO). In conclusion, the data from this study suggests that melatonin attenuates oxidative stress, which is the primary mechanism responsible for Ni-induced neurotoxicity. Considering that the hippocampus is the main structure involved in the pathology associated with heavy metal intoxication, such as Ni, these findings underscore the potential therapeutic efficacy of melatonin in mitigating heavy metal-induced brain damage.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"28 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560986","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}