Neurotoxicity Research最新文献

{"title":"Effect of Cannabidiol in LPS-Induced Toxicity in Astrocytes: Possible Role for Cannabinoid Type-1 Receptors.","authors":"Hind Ibork, Sara El Idrissi, Simo Siyanda Zulu, Robert Miller, Lhoussain Hajji, Annabelle Manalo Morgan, Khalid Taghzouti, Oualid Abboussi","doi":"10.1007/s12640-023-00671-2","DOIUrl":"10.1007/s12640-023-00671-2","url":null,"abstract":"<p><p>Cerebral metabolic abnormalities are common in neurodegenerative diseases. Previous studies have shown that mitochondrial damage alters ATP production and increases reactive oxygen species (ROS) release which may contribute to neurodegeneration. In the present study, we investigated the neuroprotective effects of cannabidiol (CBD), a non-psychoactive component derived from marijuana (Cannabis sativa L.), on astrocytic bioenergetic balance in a primary cell culture model of lipopolysaccharide (LPS)-induced neurotoxicity. Astrocytic metabolic profiling using an extracellular flux analyzer demonstrated that CBD decreases mitochondrial proton leak, increased spare respiratory capacity and coupling efficiency in LPS-stimulated astrocytes. Simultaneously, CBD increased astrocytic glycolytic capacity and glycolysis reserve in a cannabinoid receptor type 1 (CB1)-dependent manner. CBD-restored metabolic changes were correlated with a significant decrease in the pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) concentration and reduction of ROS production in LPS-stimulated astrocytes. These results suggest that CBD may inhibit LPS-induced metabolic impairments and inflammation by enhancing astrocytic metabolic glycolysis versus oxidative phosphorylation through its action on CB1 receptors. The present findings suggest CBD as a potential anti-inflammatory treatment in metabolic pathologies and highlight a possible role for the cannabinoidergic system in the modulation of mitochondrial oxidative stress. CBD enhances mitochondrial bioenergetic profile, attenuates proinflammatory cytokines release, and ROS overproduction of astrocytes stimulated by LPS. These effects are not mediated directly by CB1 receptors, while these receptors seem to have a key role in the anti-inflammatory response of the endocannabinoid system on astrocytes, as their specific inhibition by SR141716A led to increased pro-inflammatory cytokines release and ROS production. The graphical abstract is created with BioRender.com.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"615-626"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41146408","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":"(m) RVD-hemopressin (α) Ameliorated Oxidative Stress, Apoptosis and Damage to the BDNF/TrkB/Akt Pathway Induced by Scopolamine in HT22 Cells.","authors":"Ruisan Zhang, Xinliang He, Jianghong Cheng, Xiaofan Zhang, Chen Han, Yifan Liu, Peng Chen, Yang Wang","doi":"10.1007/s12640-023-00677-w","DOIUrl":"10.1007/s12640-023-00677-w","url":null,"abstract":"<p><p>Dysfunction in the cholinergic system and oxidative stress are closely related and play roles in Alzheimer's disease (AD). Scopolamine (Scop), which is commonly used to induce cholinergic system damage in cells and animals, also evokes oxidative stress. Our previous study indicated that the peptide (m) RVD-hemopressin (RVD) reversed the memory-impairing effect of Scop in mice by activating cannabinoid receptor 1 (CBR1), but the mechanism was unclear. In this study, we found that RVD inhibited the oxidative stress, apoptosis, decreased cell viability and downregulation of synapse-associated proteins induced by Scop in HT22 cells. The effect was associated with the BDNF/TrkB/Akt pathway, and the effects of RVD outlined above could be blocked by an antagonist of CBR1. These results suggest that RVD may be a potential drug candidate for disorders associated with damage to the cholinergic system and oxidative stress, such as AD.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"627-637"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398480","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":"RNA-Binding Proteins: A Role in Neurotoxicity?","authors":"Andrea Ocharán-Mercado, Jaqueline Loaeza-Loaeza, Yaneth Castro-Coronel, Leonor C Acosta-Saavedra, Luisa C Hernández-Kelly, Daniel Hernández-Sotelo, Arturo Ortega","doi":"10.1007/s12640-023-00669-w","DOIUrl":"10.1007/s12640-023-00669-w","url":null,"abstract":"<p><p>Despite sustained efforts to treat neurodegenerative diseases, little is known at the molecular level to understand and generate novel therapeutic approaches for these malignancies. Therefore, it is not surprising that neurogenerative diseases are among the leading causes of death in the aged population. Neurons require sophisticated cellular mechanisms to maintain proper protein homeostasis. These cells are generally sensitive to loss of gene expression control at the post-transcriptional level. Post-translational control responds to signals that can arise from intracellular processes or environmental factors that can be regulated through RNA-binding proteins. These proteins recognize RNA through one or more RNA-binding domains and form ribonucleoproteins that are critically involved in the regulation of post-transcriptional processes from splicing to the regulation of association of the translation machinery allowing a relatively rapid and precise modulation of the transcriptome. Neurotoxicity is the result of the biological, chemical, or physical interaction of agents with an adverse effect on the structure and function of the central nervous system. The disruption of the proper levels or function of RBPs in neurons and glial cells triggers neurotoxic events that are linked to neurodegenerative diseases such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), fragile X syndrome (FXS), and frontotemporal dementia (FTD) among many others. The connection between RBPs and neurodegenerative diseases opens a new landscape for potentially novel therapeutic targets for the intervention of these neurodegenerative pathologies. In this contribution, a summary of the recent findings of the molecular mechanisms involved in the plausible role of RBPs in RNA processing in neurodegenerative disease is discussed.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"681-697"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167568","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":"Monoacylglycerol Lipase Inhibition Prevents Short-Term Mitochondrial Dysfunction and Oxidative Damage in Rat Brain Synaptosomal/Mitochondrial Fractions and Cortical Slices: Role of Cannabinoid Receptors.","authors":"Karen Jaqueline Paredes-Ruiz, Karla Chavira-Ramos, Sonia Galvan-Arzate, Edgar Rangel-López, Çimen Karasu, Isaac Túnez, Anatoly V Skalny, Tao Ke, Michael Aschner, Mario Orozco-Morales, Ana Laura Colín-González, Abel Santamaría","doi":"10.1007/s12640-023-00661-4","DOIUrl":"10.1007/s12640-023-00661-4","url":null,"abstract":"<p><p>Inhibition of enzymes responsible for endocannabinoid hydrolysis represents an invaluable emerging tool for the potential treatment of neurodegenerative disorders. Monoacylglycerol lipase (MAGL) is the enzyme responsible for degrading 2-arachydonoylglycerol (2-AG), the most abundant endocannabinoid in the central nervous system (CNS). Here, we tested the effects of the selective MAGL inhibitor JZL184 on the 3-nitropropinic acid (3-NP)-induced short-term loss of mitochondrial reductive capacity/viability and oxidative damage in rat brain synaptosomal/mitochondrial fractions and cortical slices. In synaptosomes, while 3-NP decreased mitochondrial function and increased lipid peroxidation, JZL184 attenuated both markers. The protective effects evoked by JZL184 on the 3-NP-induced mitochondrial dysfunction were primarily mediated by activation of cannabinoid receptor 2 (CB2R), as evidenced by their inhibition by the selective CB2R inverse agonist JTE907. The cannabinoid receptor 1 (CB1R) also participated in this effect in a lesser extent, as evidenced by the CB1R antagonist/inverse agonist AM281. In contrast, activation of CB1R, but not CB2R, was responsible for the protective effects of JZL184 on the 3-NP-iduced lipid peroxidation. Protective effects of JZL184 were confirmed in other toxic models involving excitotoxicity and oxidative damage as internal controls. In cortical slices, JZL184 ameliorated the 3-NP-induced loss of mitochondrial function, the increase in lipid peroxidation, and the inhibition of succinate dehydrogenase (mitochondrial complex II) activity, and these effects were independent on CB1R and CB2R, as evidenced by the lack of effects of AM281 and JTE907, respectively. Our novel results provide experimental evidence that the differential protective effects exerted by JZL184 on the early toxic effects induced by 3-NP in brain synaptosomes and cortical slices involve MAGL inhibition, and possibly the subsequent accumulation of 2-AG. These effects involve pro-energetic and redox modulatory mechanisms that may be either dependent or independent of cannabinoid receptors' activation.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"514-525"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9827414","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":"Potential Key Proteins, Molecular Networks, and Pathways in Perinatal Hypoxia.","authors":"Johann Gross, Mario Herrera-Marschitz","doi":"10.1007/s12640-023-00663-2","DOIUrl":"10.1007/s12640-023-00663-2","url":null,"abstract":"<p><p>Perinatal hypoxia is a common risk factor for CNS development. Using bioinformatics databases, a list of 129 genes involved in perinatal hypoxia was selected from the literature and analyzed with respect to proteins important for biological processes influencing the brain development. Functional enrichment analysis using the DAVID database was performed to identify relevant Gene Ontology (GO) biological processes like response to hypoxia, inflammatory response, positive and negative regulation of apoptosis, and positive and negative regulation of cell proliferation. The selected GO processes contain 17-30 proteins and show an enrichment of 6.3-14.3-fold. The STRING protein-protein interaction network and the Cytoscape data analyzer were used to identify interacting proteins playing a significant role in these processes. The two top protein pairs referring to the proteins with highest degrees and the corresponding proteins connected by high score edges exert opposite or regulatory functions and are essential for the balance between damaging, repairing, protective, or epigenetic processes. The GO response to hypoxia is characterized by the high score protein-protein interaction pairs CASP3/FAS promoting apoptosis and by the protective acting BDNF/MECP2 protein pair. Core components of the GO processes positive and negative regulation of apoptosis are the proteins CASP3/FAS/AKT/eNOS/RPS6KB1 involved in several signal pathways. The GO processes cell proliferation are characterized by the high-score protein-protein interaction pairs MYC/ MAPK1, JUN/MAPK1, IL6/IL1B, and JUN/HDAC1. The study provides new insights into the pathophysiology of perinatal hypoxia and is of importance for future investigations, diagnostics, and therapy of perinatal hypoxia.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"571-588"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123454","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":"Neuroprotective Potential of Tannic Acid Against Neurotoxic Outputs of Monosodium Glutamate in Rat Cerebral Cortex.","authors":"Medine Sibel Karagac, Hamid Ceylan","doi":"10.1007/s12640-023-00667-y","DOIUrl":"10.1007/s12640-023-00667-y","url":null,"abstract":"<p><p>Glutamate in monosodium glutamate (MSG), which is widely used in the food industry, has an important role in major brain functions such as memory, learning, synapse formation, and stabilization. However, extensive use of MSG has been linked with neurotoxicity. Therefore, in addition to clarifying the underlying mechanisms of MSG-induced neurotoxicity, it is also important to determine safe agents that can diminish the damage caused by MSG. Tannic acid (TA) is a naturally occurring plant polyphenol that exhibits versatile physiological effects such as anti-inflammatory, anti-carcinogenic, antioxidant, and radical scavenging. This study was conducted to assess the neurotoxic and neuroprotective effects of these two dietary components in the rat cerebral cortex. Twenty-four Sprague Dawley rats were divided into 4 equal groups and were treated with MSG (2 g/kg) and TA (50 mg/kg) alone and in combination for 3 weeks. Alterations in oxidative stress indicators (MDA and GSH) were measured in the cortex tissues. In addition, changes in enzymatic activities and gene expression patterns of antioxidant system components (GST, GPx, CAT, and SOD) were investigated. Furthermore, mRNA expressions of FoxO transcription factors (Foxo1 and Foxo3) and apoptotic markers (Casp3 and Casp9) were assessed. Results revealed that dietary TA intake significantly rehabilitated MSG-induced dysregulation in cortical tissue by regulating redox balance, cellular homeostasis, and apoptosis. The present study proposes that MSG-induced detrimental effects on cortical tissue are potentially mitigated by TA via modulation of oxidative stress, cell metabolism, and programmed cell death.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"670-680"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10244330","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: The Antiepileptic Drug Levetiracetam Protects Against Quinolinic Acid-Induced Toxicity in the Rat Striatum.","authors":"Maricela Dircio-Bautista,&nbsp;Ana Laura Colín-González,&nbsp;Gabriela Aguilera,&nbsp;Marisol Maya-López,&nbsp;Juana Villeda Hernández,&nbsp;Sonia Galván-Arzate,&nbsp;Esperanza García,&nbsp;Isaac Túnez,&nbsp;Abel Santamaría","doi":"10.1007/s12640-023-00659-y","DOIUrl":"10.1007/s12640-023-00659-y","url":null,"abstract":"","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"499"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567838","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: Modulatory Role of Curcumin on Cobalt‑Induced Memory Deficit, Hippocampal Oxidative Damage, Astrocytosis, and Nrf2 Expression.","authors":"Rademene S Oria,&nbsp;Godson E Anyanwu,&nbsp;Emmanuel A Esom,&nbsp;Johnson N Nto,&nbsp;Amechi U Katchy,&nbsp;Augustine U Agu,&nbsp;Omamuyovwi M Ijomone","doi":"10.1007/s12640-023-00662-3","DOIUrl":"10.1007/s12640-023-00662-3","url":null,"abstract":"","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"497-498"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10218026","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":"A Review on the Neurotoxic Effects of Doxorubicin.","authors":"Katarzyna Kamińska,&nbsp;Agnieszka Cudnoch-Jędrzejewska","doi":"10.1007/s12640-023-00652-5","DOIUrl":"10.1007/s12640-023-00652-5","url":null,"abstract":"<p><p>Anthracyclines, a class of drugs considered as most effective anticancer drugs, used in the various regimens of cancer chemotherapy, induce long-term impairment of mitochondrial respiration, increase reactive oxygen species, and induce other mechanisms potentially leading to neurotoxicity. According to literature findings, one drug of this class - doxorubicin used to treat e.g. breast cancer, bladder cancer, lymphoma, and acute lymphocytic leukemia may induce such effects in the nervous system. Doxorubicin has poor penetration into the brain due to the lack of drug penetration through the blood-brain barrier, thus the toxicity of this agent is the result of its peripheral action. This action is manifested by cognitive impairment and anatomical changes in the brain and peripheral nervous system found in both preclinical and clinical studies in adult patients. Furthermore, more than 50% of children with cancer are treated with anthracyclines including doxorubicin, which may affect their nervous system, and lead to lifelong damage in many areas of their life. Despite ongoing research into the side effects of this drug, the mechanism of its neurotoxicity action on the central and peripheral nervous system is still not well understood. This review aims to summarize the neurotoxic effects of doxorubicin in preclinical (in vitro and in vivo) research and in clinical studies. Furthermore, it discusses the possible mechanisms of the toxic action of this agent on the nervous system.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"383-397"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10249893","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":"In Silico Interactions of Natural and Synthetic Compounds with Key Proteins Involved in Alzheimer's Disease: Prospects for Designing New Therapeutics Compound.","authors":"Mehran Ebrahimi Shah-Abadi,&nbsp;Armin Ariaei,&nbsp;Fatemeh Moradi,&nbsp;Auob Rustamzadeh,&nbsp;Rastegar Rahmani Tanha,&nbsp;Nader Sadigh,&nbsp;Mohsen Marzban,&nbsp;Mahdi Heydari,&nbsp;Vahid Tavakolian Ferdousie","doi":"10.1007/s12640-023-00648-1","DOIUrl":"10.1007/s12640-023-00648-1","url":null,"abstract":"<p><p>Memory impairment is a result of multiple factors including amyloid-beta (Aβ) accumulation. Several receptors are mediated for Aβ transport and signaling. Moreover, blood lipids are involved in Aβ signaling pathway through these receptors. Mediated blood lipid level by statins aims to regulate Aβ signaling cascade. First, the structure of receptors was taken from the RCSB PDB database and prepared with MGLTools and AutoDock tool 4. Second, the ligand was prepared for docking through AutoDock Vina. The binding affinity was calculated, and the binding sites were determined through LigPlot+ software. Besides, pharmacokinetic properties were calculated through multiple software. Finally, a molecular dynamics (MD) simulation was conducted to evaluate ligands stability along with clustering analysis to evaluate proteins connection. Our molecular docking and dynamic analyses revealed silymarin as a potential inhibitor of acetylcholinesterase (AChE), P-glycoprotein, and angiotensin-converting enzyme 2 (ACE2) with 0.704, 0.85, and 0.83 Å for RMSD along with -114.27, -107.44, and -122.51 kcal/mol for free binding energy, respectively. Moreover, rosuvastatin and quercetin have more stability compared to silymarin and donepezil in complex with P-glycoprotein and ACE2, respectively. Eventually, based on clustering and pharmacokinetics analysis, silymarin, rosuvastatin, and quercetin are suggested to be involved in peripheral clearance of Aβ. The bioactivity effects of mentioned statins and antioxidants are predicted to be helpful in treating memory impairment in Alzheimer's disease (AD). Nevertheless, mentioned drug effect could be improved by nanoparticles to facilitate penetration of the blood-brain barrier (BBB).</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"408-430"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230057","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}