ACS Chemical Neuroscience最新文献

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Structure-Activity Relationships of the Fentanyl Scaffold: Identification of Antagonists as Potential Opioid Overdose Reversal Agents. 芬太尼支架的结构-活性关系:鉴定作为潜在阿片类药物过量逆转剂的拮抗剂。
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-12 DOI: 10.1021/acschemneuro.4c00203
Jessica P Anand, Sierra C Moore, Emma E Dixon, Carmelita M Perrien Naccarato, Joshua L West, Lennon J Delong, Emily Burgess, Jack J Twarozynski, John R Traynor
{"title":"Structure-Activity Relationships of the Fentanyl Scaffold: Identification of Antagonists as Potential Opioid Overdose Reversal Agents.","authors":"Jessica P Anand, Sierra C Moore, Emma E Dixon, Carmelita M Perrien Naccarato, Joshua L West, Lennon J Delong, Emily Burgess, Jack J Twarozynski, John R Traynor","doi":"10.1021/acschemneuro.4c00203","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00203","url":null,"abstract":"<p><p>Opioid-related overdoses account for almost half of all drug overdose deaths in the United States and cause more preventable deaths every year than car crashes. Fentanyl, a highly potent mu opioid receptor (MOR) agonist and its analogues (fentalogues) are increasingly found in illicit drug samples, both where the primary drug of abuse is an opioid and where it is not. The prevalence of fentalogues in the illicit drug market is thought to be the primary driver of the increased number of opioid-related overdose deaths since 2016. In fact, fentanyl and its analogues are involved in more than 70% of opioid-related overdoses. The standard opioid overdose rescue therapy naloxone is often insufficient to reverse opioid overdoses caused by fentalogue agonists under current treatment paradigms. However, the pharmacology of many fentalogues is unknown. Moreover, within the fentalogue series of compounds, it is possible that antagonists could be identified that might be superior to naloxone as opioid overdose reversal agents. In this report, we explore the pharmacology of 70 fentalogues and identify compounds that behave as MOR antagonists in vitro and demonstrate with one of these reversals of fentanyl-induced respiratory depression in the mouse. Such compounds could provide leads for the development of effective agents for the reversal of opioid overdose.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588884","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}
引用次数: 0
Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration. 多谷氨酰胺(PolyQ)疾病:导航神经退行性疾病。
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-12 DOI: 10.1021/acschemneuro.4c00184
Rumiana Tenchov, Janet M Sasso, Qiongqiong Angela Zhou
{"title":"Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration.","authors":"Rumiana Tenchov, Janet M Sasso, Qiongqiong Angela Zhou","doi":"10.1021/acschemneuro.4c00184","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00184","url":null,"abstract":"<p><p>Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally expanded polyglutamine tract. A total of nine polyQ disorders have been identified, including Huntington's disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA). The diseases of this class are each considered rare, yet polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. While each subtype of polyQ diseases has its own causative gene, certain pathologic molecular attributes have been implicated in virtually all of the polyQ diseases, including protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, and mitochondrial dysfunction. Although animal models of polyQ disease are available helping to understand their pathogenesis and access disease-modifying therapies, there is neither a cure nor prevention for these diseases, with only symptomatic treatments available. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in the class of polyQ diseases. We examine the publication landscape in the area in effort to provide insights into current knowledge advances and developments. We review the most discussed concepts and assess the strategies to combat these diseases. Finally, we inspect clinical applications of products against polyQ diseases with their development pipelines. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding the class of polyQ diseases, to outline challenges, and evaluate growth opportunities to further efforts in combating the diseases.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597895","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}
引用次数: 0
Machine Learned Classification of Ligand Intrinsic Activities at Human μ-Opioid Receptor. 人μ-阿片受体配体内在活性的机器学习分类。
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-11 DOI: 10.1021/acschemneuro.4c00212
Myongin Oh, Maximilian Shen, Ruibin Liu, Lidiya Stavitskaya, Jana Shen
{"title":"Machine Learned Classification of Ligand Intrinsic Activities at Human μ-Opioid Receptor.","authors":"Myongin Oh, Maximilian Shen, Ruibin Liu, Lidiya Stavitskaya, Jana Shen","doi":"10.1021/acschemneuro.4c00212","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00212","url":null,"abstract":"<p><p>Opioids are small-molecule agonists of μ-opioid receptor (μOR), while reversal agents such as naloxone are antagonists of μOR. Here, we developed machine learning (ML) models to classify the intrinsic activities of ligands at the human μOR based on the SMILES strings and two-dimensional molecular descriptors. We first manually curated a database of 983 small molecules with measured <i>E</i><sub>max</sub> values at the human μOR. Analysis of the chemical space allowed identification of dominant scaffolds and structurally similar agonists and antagonists. Decision tree models and directed message passing neural networks (MPNNs) were then trained to classify agonistic and antagonistic ligands. The hold-out test AUCs (areas under the receiver operator curves) of the extra-tree (ET) and MPNN models are 91.5 ± 3.9% and 91.8 ± 4.4%, respectively. To overcome the challenge of a small data set, a student-teacher learning method called tritraining with disagreement was tested using an unlabeled data set comprised of 15,816 ligands of human, mouse, and rat μOR, κOR, and δOR. We found that the tritraining scheme was able to increase the hold-out AUC of MPNN models to as high as 95.7%. Our work demonstrates the feasibility of developing ML models to accurately predict the intrinsic activities of μOR ligands, even with limited data. We envisage potential applications of these models in evaluating uncharacterized substances for public safety risks and discovering new therapeutic agents to counteract opioid overdoses.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588883","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}
引用次数: 0
Electroencephalographic and Behavioral Effects of Intranasal Administration of a Na+, K+-ATPase-Activating Antibody after Status Epilepticus. 癫痫状态后鼻内注射 Na+、K+-ATP 酶激活抗体的脑电图和行为效应
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-11 DOI: 10.1021/acschemneuro.4c00141
Fernanda Kulinski Mello, Tuane Bazanella Sampaio, Bruna Neuberger, Michele Pereira Mallmann, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, James W Larrick, Mauro Schneider Oliveira
{"title":"Electroencephalographic and Behavioral Effects of Intranasal Administration of a Na<sup>+</sup>, K<sup>+</sup>-ATPase-Activating Antibody after Status Epilepticus.","authors":"Fernanda Kulinski Mello, Tuane Bazanella Sampaio, Bruna Neuberger, Michele Pereira Mallmann, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, James W Larrick, Mauro Schneider Oliveira","doi":"10.1021/acschemneuro.4c00141","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00141","url":null,"abstract":"<p><p>Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na<sup>+</sup>, K<sup>+</sup>-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na<sup>+</sup>, K<sup>+</sup>-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE. Rats were submitted to pilocarpine-induced SE, followed by intranasal administration (2 μg/nostril). The antibody increased EEG activity following SE, namely, EEG power in theta, beta, and gamma frequency bands, assessed by quantitative analysis of EEG power spectra. One week later, DRRSAb-treated animals displayed less behavioral hyperreactivity in pick-up tests and better performance in novel object recognition tests, indicating that the intranasal administration of this Na<sup>+</sup>, K<sup>+</sup>-ATPase activator immediately after SE improves behavioral outcomes at a later time point. These results suggest that Na<sup>+</sup>, K<sup>+</sup>-ATPase activation warrants further investigation as an adjunctive therapeutic strategy for SE.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578191","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}
引用次数: 0
Design, Synthesis, and Evaluation of a Novel Conjugate Molecule with Dopaminergic and Neuroprotective Activities for Parkinson's Disease. 设计、合成和评估具有多巴胺能和神经保护活性的新型帕金森病共轭分子。
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-11 DOI: 10.1021/acschemneuro.4c00169
Diego Ploper, Agustín O Pernicone, Rodrigo H Tomas-Grau, Verónica E Manzano, Sergio B Socías, María Del Milagro Teran, Valentina Budeguer Isa, Bernardo Sosa-Padilla, Florencia González-Lizárraga, César L Avila, María Laura Guayán, Silvina Chaves, Hernán Cruz, Esteban Vera Pingitore, Oscar Varela, Rosana Chehín
{"title":"Design, Synthesis, and Evaluation of a Novel Conjugate Molecule with Dopaminergic and Neuroprotective Activities for Parkinson's Disease.","authors":"Diego Ploper, Agustín O Pernicone, Rodrigo H Tomas-Grau, Verónica E Manzano, Sergio B Socías, María Del Milagro Teran, Valentina Budeguer Isa, Bernardo Sosa-Padilla, Florencia González-Lizárraga, César L Avila, María Laura Guayán, Silvina Chaves, Hernán Cruz, Esteban Vera Pingitore, Oscar Varela, Rosana Chehín","doi":"10.1021/acschemneuro.4c00169","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00169","url":null,"abstract":"<p><p>The escalating prevalence of Parkinson's disease (PD) underscores the need for innovative therapeutic interventions since current palliative measures, including the standard l-Dopa formulations, face challenges of tolerance and side effects while failing to address the underlying neurodegenerative processes. Here, we introduce <b>DAD9</b>, a novel conjugate molecule that aims to combine symptomatic relief with disease-modifying strategies for PD. Crafted through knowledge-guided chemistry, the molecule combines a nonantibiotic doxycycline derivative with dopamine, preserving neuroprotective attributes while maintaining dopaminergic agonism. This compound exhibited no off-target effects on PD-relevant cell functions and sustained antioxidant and anti-inflammatory properties of the tetracycline precursor. Furthermore, it effectively interfered with the formation and seeding of toxic α-synuclein aggregates without producing detrimental oxidative species. In addition, <b>DAD9</b> was able to activate dopamine receptors, and docking simulations shed light onto the molecular details of this interaction. These findings position <b>DAD9</b> as a potential neuroprotective dopaminergic agonist, promising advancements in PD therapeutics.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588882","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}
引用次数: 0
Correction to "Menthol-Modified Quercetin Liposomes with Brain-Targeting Function for the Treatment of Senescent Alzheimer's Disease". 具有脑靶向功能的薄荷改性槲皮素脂质体用于治疗老年性阿尔茨海默病》的更正。
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-10 DOI: 10.1021/acschemneuro.4c00398
Wan-Ying Liu, Yang Yu, Juan Zang, Yang Liu, Feng-Rui Li, Lu Zhang, Rui-Bo Guo, Liang Kong, Ling-Yue Ma, Xue-Tao Li
{"title":"Correction to \"Menthol-Modified Quercetin Liposomes with Brain-Targeting Function for the Treatment of Senescent Alzheimer's Disease\".","authors":"Wan-Ying Liu, Yang Yu, Juan Zang, Yang Liu, Feng-Rui Li, Lu Zhang, Rui-Bo Guo, Liang Kong, Ling-Yue Ma, Xue-Tao Li","doi":"10.1021/acschemneuro.4c00398","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00398","url":null,"abstract":"","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578190","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}
引用次数: 0
Preparation and Characterization of Zn(II)-Stabilized Aβ42 Oligomers. Zn(II)-Stabilized Aβ42 低聚物的制备与表征。
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-09 DOI: 10.1021/acschemneuro.4c00084
Alicia González Díaz, Rodrigo Cataldi, Benedetta Mannini, Michele Vendruscolo
{"title":"Preparation and Characterization of Zn(II)-Stabilized Aβ<sub>42</sub> Oligomers.","authors":"Alicia González Díaz, Rodrigo Cataldi, Benedetta Mannini, Michele Vendruscolo","doi":"10.1021/acschemneuro.4c00084","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00084","url":null,"abstract":"<p><p>Aβ oligomers are being investigated as cytotoxic agents in Alzheimer's disease (AD). Because of their transient nature and conformational heterogeneity, the relationship between the structure and activity of these oligomers is still poorly understood. Hence, methods for stabilizing Aβ oligomeric species relevant to AD are needed to uncover the structural determinants of their cytotoxicity. Here, we build on the observation that metal ions and metabolites have been shown to interact with Aβ, influencing its aggregation and stabilizing its oligomeric species. We thus developed a method that uses zinc ions, Zn(II), to stabilize oligomers produced by the 42-residue form of Aβ (Aβ<sub>42</sub>), which is dysregulated in AD. These Aβ<sub>42</sub>-Zn(II) oligomers are small in size, spanning the 10-30 nm range, stable at physiological temperature, and with a broad toxic profile in human neuroblastoma cells. These oligomers offer a tool to study the mechanisms of toxicity of Aβ oligomers in cellular and animal AD models.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557351","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}
引用次数: 0
Harnessing the Therapeutic Potential of Peptides for Synergistic Treatment of Alzheimer's Disease by Targeting Aβ Aggregation, Metal-Mediated Aβ Aggregation, Cholinesterase, Tau Degradation, and Oxidative Stress. 通过靶向 Aβ 聚集、金属介导的 Aβ 聚集、胆碱酯酶、Tau 降解和氧化应激,利用肽的治疗潜力协同治疗阿尔茨海默病。
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-09 DOI: 10.1021/acschemneuro.4c00246
Kamaljot Singh, Anupamjeet Kaur, Bhupesh Goyal, Deepti Goyal
{"title":"Harnessing the Therapeutic Potential of Peptides for Synergistic Treatment of Alzheimer's Disease by Targeting Aβ Aggregation, Metal-Mediated Aβ Aggregation, Cholinesterase, Tau Degradation, and Oxidative Stress.","authors":"Kamaljot Singh, Anupamjeet Kaur, Bhupesh Goyal, Deepti Goyal","doi":"10.1021/acschemneuro.4c00246","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00246","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive multifaceted neurodegenerative disease and remains a formidable global health challenge. The current medication for AD gives symptomatic relief and, thus, urges us to look for alternative disease-modifying therapies based on a multitarget directed approach. Looking at the remarkable progress made in peptide drug development in the last decade and the benefits associated with peptides, they offer valuable chemotypes [multitarget directed ligands (MTDLs)] as AD therapeutics. This review recapitulates the current developments made in harnessing peptides as MTDLs in combating AD by targeting multiple key pathways involved in the disease's progression. The peptides hold immense potential and represent a convincing avenue in the pursuit of novel AD therapeutics. While hurdles remain, ongoing research offers hope that peptides may eventually provide a multifaceted approach to combat AD.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557350","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}
引用次数: 0
Targeting Microglial Immunoproteasome: A Novel Approach in Neuroinflammatory-Related Disorders. 靶向小胶质细胞免疫蛋白酶体:治疗神经炎症相关疾病的新方法
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-06 DOI: 10.1021/acschemneuro.4c00099
Natalia Malek, Radoslaw Gladysz, Natalia Stelmach, Marcin Drag
{"title":"Targeting Microglial Immunoproteasome: A Novel Approach in Neuroinflammatory-Related Disorders.","authors":"Natalia Malek, Radoslaw Gladysz, Natalia Stelmach, Marcin Drag","doi":"10.1021/acschemneuro.4c00099","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00099","url":null,"abstract":"<p><p>It is widely acknowledged that the aging process is linked to the accumulation of damaged and misfolded proteins. This phenomenon is accompanied by a decrease in proteasome (c20S) activity, concomitant with an increase in immunoproteasome (i20S) activity. These changes can be attributed, in part, to the chronic neuroinflammation that occurs in brain tissues. Neuroinflammation is a complex process characterized by the activation of immune cells in the central nervous system (CNS) in response to injury, infection, and other pathological stimuli. In certain cases, this immune response becomes chronic, contributing to the pathogenesis of various neurological disorders, including chronic pain, Alzheimer's disease, Parkinson's disease, brain traumatic injury, and others. Microglia, the resident immune cells in the brain, play a crucial role in the neuroinflammatory response. Recent research has highlighted the involvement of i20S in promoting neuroinflammation, increased activity of which may lead to the presentation of self-antigens, triggering an autoimmune response against the CNS, exacerbating inflammation, and contributing to neurodegeneration. Furthermore, since i20S plays a role in breaking down accumulated proteins during inflammation within the cell body, any disruption in its activity could lead to a prolonged state of inflammation and subsequent cell death. Given the pivotal role of i20S in neuroinflammation, targeting this proteasome subtype has emerged as a potential therapeutic approach for managing neuroinflammatory diseases. This review delves into the mechanisms of neuroinflammation and microglia activation, exploring the potential of i20S inhibitors as a promising therapeutic strategy for managing neuroinflammatory disorders.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544142","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}
引用次数: 0
MiR-23b-3p Improves Brain Damage after Status Epilepticus by Reducing the Formation of Pathological High-Frequency Oscillations via Inhibition of cx43 in Rat Hippocampus. MiR-23b-3p 通过抑制大鼠海马的 cx43 减少病理性高频振荡的形成,从而改善癫痫状态后的脑损伤
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2024-07-05 DOI: 10.1021/acschemneuro.4c00112
Yanjun Yi, Shimin Zhang, Jiali Dai, Hao Zheng, Xiaoling Peng, Li Cheng, Hengsheng Chen, Yue Hu
{"title":"MiR-23b-3p Improves Brain Damage after Status Epilepticus by Reducing the Formation of Pathological High-Frequency Oscillations via Inhibition of cx43 in Rat Hippocampus.","authors":"Yanjun Yi, Shimin Zhang, Jiali Dai, Hao Zheng, Xiaoling Peng, Li Cheng, Hengsheng Chen, Yue Hu","doi":"10.1021/acschemneuro.4c00112","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00112","url":null,"abstract":"<p><p>In order to investigate the effectiveness and safety of miR-23b-3p in anti-seizure activity and to elucidate the regulatory relationship between miR-23b-3p and Cx43 in the nervous system, we have established a lithium chloride-pilocarpine (PILO) status epilepticus (SE) model. Rats were randomly divided into the following groups: seizure control (PILO), valproate sodium (VPA+PILO), recombinant miR-23b-3p overexpression (miR+PILO), miR-23b-3p sponges (Sponges+PILO), and scramble sequence negative control (Scramble+PILO) (n = 6/group). After experiments, we got the following results. In the acute phase, the time required for rats to reach stage IV after PILO injection was significantly longer in VPA+PILO and miR+PILO. In the chronic phase after SE, the frequency of spontaneous recurrent seizures (SRSs) in VPA+PILO and miR+PILO was significantly reduced. At 10 min before seizure cessation, the average energy expression of fast ripples (FRs) in VPA+PILO and miR+PILO was significantly lower than in PILO. After 28 days of seizure, Cx43 expression in PILO was significantly increased, and Beclin1expression in all groups was significantly increased. After 28 days of SE,the number of synapses in the CA1 region of the hippocampus was significantly higher in the VPA+PILO and miR+PILO groups compared to that in the PILO group. After 28 days of SE ,hippocampal necrotic cells in the CA3 region were significantly lower in the VPA+PILO and miR+PILO groups compared to those in the PILO group. There were no significant differences in biochemical indicators among the experimental group rats 28 days after SE compared to the seizure control group. Based on the previous facts, we can reach the conclusion that MiR-23b-3p targets and blocks the expression of hippocampal Cx43 which can reduce the formation of pathological FRs, thereby alleviating the severity of seizures, improving seizure-induced brain damage.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141532866","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}
引用次数: 0
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