Neurotoxicity Research最新文献

{"title":"E2F1 Mediates Traumatic Brain Injury and Regulates BDNF-AS to Promote the Progression of Alzheimer’s Disease","authors":"Yuting Ding, Wenkang Luan, Xuanlin Shen, Zhe Wang, Yongjun Cao","doi":"10.1007/s12640-024-00695-2","DOIUrl":"https://doi.org/10.1007/s12640-024-00695-2","url":null,"abstract":"<p>Traumatic brain injury (TBI) is one of the important risk factors for the development of Alzheimer’s disease (AD). However, the molecular mechanism by which TBI promotes the progression of AD is not elucidated. In this study, we showed that the abnormal production of E2F1 is a major factor in promoting the neuropathological and cognitive deterioration of AD post-TBI. We found that repeated mild TBI can aggravate the neuropathology of AD in APP/PS1 mice. At the same time, the co-expression of E2F1 and beta-site APP cleaving enzyme 1 (BACE1) was upregulated when the mouse hippocampus was dissected. BACE1 is recognized as a rate-limiting enzyme for the production of Aβ. Here, we speculate that E2F1 may play a role in promoting BACE1 expression in AD. Therefore, we collected peripheral blood from patients with AD. Interestingly, there is a positive correlation between E2F1 and brain-derived neurotrophic factor–antisense (BDNF-AS), whereas BDNF-AS in AD can promote the expression of BACE1 and exhibit a neurotoxic effect. We established a cell model and found a regulatory relationship between E2F1 and BDNF-AS. Therefore, based on our results, we concluded that E2F1 regulates BDNF-AS, promotes the expression of BACE1, and affects the progression of AD. Furthermore, E2F1 mediates the TBI-induced neurotoxicity of AD.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"39 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139918393","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":"Molecular Docking Analysis at the Human α7-nAChR and Proliferative and Evoked-Calcium Changes in SH-SY5Y Cells by Imidacloprid and Acetamiprid Insecticides.","authors":"Marcelo S Guzman-Vallejos, Lenin J Ramirez-Cando, Luis Aguayo, Santiago J Ballaz","doi":"10.1007/s12640-024-00697-0","DOIUrl":"10.1007/s12640-024-00697-0","url":null,"abstract":"<p><p>Acetamiprid (ACE) and Imidacloprid (IMI) are widely-used neonicotinoid insecticides (NNIs) with functional activity at human acetylcholine nicotinic receptors and, therefore, with putative toxic effects. The objective of this study was the evaluation of the interactions between NNIs and α7-nAChR, as this receptor keeps intracellular Ca2+ ([Ca2+]i) to an optimum for an adequate neuronal functioning. Possible interactions between NNIs and the cryo-EM structure of the human α-7 nAChR were identified by molecular docking. Additionally, NNI effects were analyzed in neuroblastoma SH-SY5Y cells, as they naturally express α-7 nAChRs. Functional studies included proliferative/cytotoxic effects (MTT test) in undifferentiated SH-SY-5Y cells and indirect measurements of [Ca2+]i transients in retinoic acid-differentiated SH-SY-5Y cells loaded with Fluo-4 AM. Docking analysis showed that the binding of IMI and ACE occurred at the same aromatic cage that the specific α-7 nAChR agonist EVP-6124. IMI showed a better docking strength than ACE. According to the MTT assays, low doses (10-50 µM) of IMI better than ACE stimulated neuroblastoma cell proliferation. At higher doses (250-500 µM), IMI also prevailed over ACE and dose-dependently triggered more abrupt fluorescence changes due to [Ca2+]i mobilization in differentiated SH-SY5Y neurons. Indeed, only IMI blunted nicotine-evoked intracellular fluorescence stimulation (i.e., nicotine cross-desensitization). Summarizing, IMI demonstrated a superior docking strength and more robust cellular responses compared to ACE, which were likely associated with a stronger activity at α-7nAChRs. Through the interaction with α-7nAChRs, IMI would demonstrate its high neurotoxic potential for humans. More research is needed for investigating the proliferative effects of IMI in neuroblastoma cells.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 2","pages":"16"},"PeriodicalIF":3.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906217","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":"METTL3 Mediates Microglial Activation and Blood-Brain Barrier Permeability in Cerebral Ischemic Stroke by Regulating NLRP3 Inflammasomes Through m6A Methylation Modification.","authors":"Xue Cheng, Zhetan Ren, Huiyang Jia, Gang Wang","doi":"10.1007/s12640-024-00687-2","DOIUrl":"10.1007/s12640-024-00687-2","url":null,"abstract":"<p><p>Cerebral ischemic stroke (CIS) is the main cause of disability. METTL3 is implicated in CIS, and we explored its specific mechanism. Middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation/reperfusion (OGD/R) HAPI cell model were established and treated with LV-METTL3 or DAA, oe-METTL3, miR-335-3p mimics, or DAA, to assess their effects on MCAO rat neurological and motor function, cerebral infarction area, brain water content, microglial activation, blood-brain barrier (BBB) permeability, and NLRP3 inflammasome activation. METTL3, pri-miR-335-3p, mature miR-335-3p, and miR-335-3p mRNA levels were assessed by RT-qPCR; M1/M2 microglial phenotype proportion and M1/M2 microglia ratio, inflammatory factor levels, and m6A modification were assessed. MCAO rats manifested cerebral ischemia injury. METTL3 was under-expressed in CIS. METTL3 overexpression inhibited microglial activation and M1 polarization and BBB permeability in MCAO rats and inhibited OGD/R-induced microglial activation and reduced M1 polarization. METTL3 regulated miR-335-3p expression and inhibited NLRP3 inflammasome activation. m6A methylation inhibition averted METTL3's effects on NLRP3 activation, thus promoting microglial activation in OGD/R-induced cells and METTL3's effects on BBB permeability in MCAO rats. Briefly, METTL3 regulated miR-335-3p expression through RNA m6A methylation and inhibited NLRP3 inflammasome activation, thus repressing microglial activation, BBB permeability, and protecting against CIS.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"15"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723421","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":"High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System.","authors":"Simone A A Romariz, Viviam Sanabria, Karina Ribeiro da Silva, Miguel L Quintella, Bruna A G de Melo, Marimélia Porcionatto, Danilo Candido de Almeida, Beatriz M Longo","doi":"10.1007/s12640-024-00692-5","DOIUrl":"10.1007/s12640-024-00692-5","url":null,"abstract":"<p><p>Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD's influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and β-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"14"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723420","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":"Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia.","authors":"Guilherme S Rieder, Marcos M Braga, Ben Hur M Mussulini, Emerson S Silva, Gabriela Lazzarotto, Emerson André Casali, Diogo L Oliveira, Jeferson L Franco, Diogo O G Souza, João Batista T Rocha","doi":"10.1007/s12640-024-00691-6","DOIUrl":"10.1007/s12640-024-00691-6","url":null,"abstract":"<p><p>Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)₂] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)₂ was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)₂ content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)₂ effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)₂ on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)₂ should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"13"},"PeriodicalIF":3.7,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707390","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":"ZNF787 and HDAC1 Mediate Blood-Brain Barrier Permeability in an In Vitro Model of Alzheimer's Disease Microenvironment.","authors":"Lu Zhang, Baicheng Zhu, Xinxin Zhou, Hao Ning, Fengying Zhang, Bingju Yan, Jiajia Chen, Teng Ma","doi":"10.1007/s12640-024-00693-4","DOIUrl":"10.1007/s12640-024-00693-4","url":null,"abstract":"<p><p>The permeability of the blood-brain barrier (BBB) is increased in Alzheimer's disease (AD). This plays a key role in the instigation and maintenance of chronic inflammation during AD. Experiments using AD models showed that the increased permeability of the BBB was mainly caused by the decreased expression of tight junction-related proteins occludin and claudin-5. In this study, we found that ZNF787 and HDAC1 were upregulated in β-amyloid (Aβ)_1-42-incubated endothelial cells, resulting in increased BBB permeability. Conversely, the silencing of ZNF787 and HDAC1 by RNAi led to reduced BBB permeability. The silencing of ZNF787 and HDAC1 enhanced the expression of occludin and claudin-5. Mechanistically, ZNF787 binds to promoter regions for occludin and claudin-5 and functions as a transcriptional regulator. Furthermore, we demonstrate that ZNF787 interacts with HDAC1, and this resulted in the downregulation of the expression of genes encoding tight junction-related proteins to increase in BBB permeability. Taken together, our study identifies critical roles for the interaction between ZNF787 and HDAC1 in regulating BBB permeability and the pathogenesis of AD.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"12"},"PeriodicalIF":3.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703037","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":"Exploring Caenorhabditis elegans as Parkinson's Disease Model: Neurotoxins and Genetic Implications.","authors":"Larissa Pereira Dantas da Silva, Erika da Cruz Guedes, Isabel Cristina Oliveira Fernandes, Lucas Aleixo Leal Pedroza, Gustavo José da Silva Pereira, Priscila Gubert","doi":"10.1007/s12640-024-00686-3","DOIUrl":"10.1007/s12640-024-00686-3","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, the first being Alzheimer's disease. Patients with PD have a loss of dopaminergic neurons in the substantia nigra of the basal ganglia, which controls voluntary movements, causing a motor impairment as a result of dopaminergic signaling impairment. Studies have shown that mutations in several genes, such as SNCA, PARK2, PINK1, DJ-1, ATP13A2, and LRRK2, and the exposure to neurotoxic agents can potentially increase the chances of PD development. The nematode Caenorhabditis elegans (C. elegans) plays an important role in studying the risk factors, such as genetic factors, aging, exposure to chemicals, disease progression, and drug treatments for PD. C. elegans has a conserved neurotransmission system during evolution; it produces dopamine, through the eight dopaminergic neurons; it can be used to study the effect of neurotoxins and also has strains that express human α-synuclein. Furthermore, the human PD-related genes, LRK-1, PINK-1, PDR-1, DJR-1.1, and CATP-6, are present and functional in this model. Therefore, this review focuses on highlighting and discussing the use of C. elegans an in vivo model in PD-related studies. Here, we identified that nematodes exposed to the neurotoxins, such as 6-OHDA, MPTP, paraquat, and rotenone, had a progressive loss of dopaminergic neurons, dopamine deficits, and decreased survival rate. Several studies have reported that expression of human LRRK2 (G2019S) caused neurodegeneration and pink-1, pdr-1, and djr-1.1 deletion caused several effects PD-related in C. elegans, including mitochondrial dysfunctions. Of note, the deletion of catp-6 in nematodes caused behavioral dysfunction, mitochondrial damage, and reduced survival. In addition, nematodes expressing α-synuclein had neurodegeneration and dopamine-dependent deficits. Therefore, C. elegans can be considered an accurate animal model of PD that can be used to elucidate to assess the underlying mechanisms implicated in PD to find novel therapeutic targets.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"11"},"PeriodicalIF":3.7,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692472","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":"Cisplatin Provokes Peripheral Nociception and Neuronal Features of Therapy-Induced Senescence and Calcium Dysregulation in Rats.","authors":"Tareq Saleh, Randa Naffa, Noor A Barakat, Mohammad A Ismail, Moureq R Alotaibi, Mohammad Alsalem","doi":"10.1007/s12640-024-00690-7","DOIUrl":"10.1007/s12640-024-00690-7","url":null,"abstract":"<p><p>Therapy-Induced Senescence (TIS) is a form of senescence that is typically described in malignant cells in response to the exposure of cancer chemotherapy or radiation but can also be precipitated in non-malignant cells. TIS has been shown to contribute to the development of several cancer therapy-related adverse effects; however, evidence on its role in mediating chemotherapy-induced neurotoxicity, such as Chemotherapy-induced Peripheral Neuropathy (CIPN), is limited. We here show that cisplatin treatment over two cycles (cumulative dose of 23 mg/kg) provoked mechanical allodynia and thermal hyperalgesia in Sprague-Dawley rats. Isolation of dorsal root ganglia (DRG) from the cisplatin-treated rats demonstrated robust SA-β-gal upregulation at both day 8 (after the first cycle) and day 18 (after the second cycle), decreased lmnb1 expression, increased expression of cdkn1a and cdkn2a, and of several factors of the Senescence-associated Secretory Phenotype (SASP) (Il6, Il1b, and mmp9). Moreover, single-cell calcium imaging of cultured DRGs revealed a significant increase in terms of the magnitude of KCl-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats. No significant change was observed in terms of the magnitude of capsaicin-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats but with decreased area under the curve of the responses in cisplatin-treated rats. Further evidence to support the contribution of TIS to therapy adverse effects is required but should encourage the use of senescence-modulating agents (senotherapeutics) as novel palliative approaches to mitigate chemotherapy-induced neurotoxicity.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"10"},"PeriodicalIF":3.7,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642595","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":"Transposable Elements: Emerging Therapeutic Targets in Neurodegenerative Diseases.","authors":"Shrishti Singh, Maheshkumar R Borkar, Lokesh Kumar Bhatt","doi":"10.1007/s12640-024-00688-1","DOIUrl":"10.1007/s12640-024-00688-1","url":null,"abstract":"<p><p>Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of neuronal function and structure. While several genetic and environmental factors have been implicated in the pathogenesis of these disorders, emerging evidence suggests that transposable elements (TEs), once considered \"junk DNA,\" play a significant role in their development and progression. TEs are mobile genetic elements capable of moving within the genome, and their dysregulation has been associated with genomic instability, altered gene expression, and neuroinflammation. This review provides an overview of TEs, including long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), and endogenous retroviruses (ERVs), mechanisms of repression and derepression, and their potential impact on neurodegeneration. The evidence linking TEs to AD, PD, and ALS by shedding light on the complex interactions between TEs and neurodegeneration has been discussed. Furthermore, the therapeutic potential of targeting TEs in neurodegenerative diseases has been explored. Understanding the role of TEs in neurodegeneration holds promise for developing novel therapeutic strategies aimed at mitigating disease progression and preserving neuronal health.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"9"},"PeriodicalIF":3.7,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547064","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":"Monoclonal Antibody Targeting CGRP Relieves Cisplatin-Induced Neuropathic Pain by Attenuating Neuroinflammation.","authors":"Shun Xie, Zhenfang Gao, Jiale Zhang, Cong Xing, Yanxin Dong, Lanyin Wang, Zhiding Wang, Yuxiang Li, Ge Li, Gencheng Han, Taiqian Gong","doi":"10.1007/s12640-023-00685-w","DOIUrl":"10.1007/s12640-023-00685-w","url":null,"abstract":"<p><p>Chemotherapy-induced neuropathic pain (CIPN) is a common side effect of antitumor chemotherapeutic agents. It describes a pathological state of pain related to the cumulative dosage of the drug, significantly limiting the efficacy of antitumor treatment. Sofas strategies alleviating CIPN still lack. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in many pathologic pains. In this study, we explored the effects of CGRP blocking on CIPN and potential mechanisms. Total dose of 20.7 mg/kg cisplatin was used to establish a CIPN mouse model. Mechanical and thermal hypersensitivity was measured using von Frey hairs and tail flick test. Western blot and immunofluorescence were utilized to evaluate the levels of CGRP and activated astrocytes in mouse spinal cord, respectively. In addition, real-time quantitative PCR (RT-qPCR) was used to detect the level of inflammatory cytokines such as IL-6, IL-1β, and NLRP3 in vitro and in vivo. There are markedly increased CGRP expression and astrocyte activation in the spinal cord of mice following cisplatin treatment. Pretreatment with a monoclonal antibody targeting CGRP (ZR8 mAb) effectively reduced cisplatin-induced mechanical hypersensitivity and thermal nociceptive sensitization and attenuated neuroinflammation as marked by downregulated expression of IL-6, IL-1β, and NLRP3 in the mice spinal cord and spleen. Lastly, ZR8 mAb does not interfere with the antitumor effects of cisplatin in tumor-bearing mice. Our findings indicate that neutralizing CGRP with monoclonal antibody could effectively alleviate CIPN by attenuating neuroinflammation. CGRP is a promising therapeutic target for CIPN.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 1","pages":"8"},"PeriodicalIF":3.7,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403811","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}