Experimental Neurobiology最新文献_第10页

Invertebrate Model Organisms as a Platform to Investigate Rare Human Neurological Diseases 无脊椎动物模型生物作为研究罕见人类神经系统疾病的平台

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-02-28 DOI: 10.5607/en22003

Ji-Hye Lee

{"title":"Invertebrate Model Organisms as a Platform to Investigate Rare Human Neurological Diseases","authors":"Ji-Hye Lee","doi":"10.5607/en22003","DOIUrl":"https://doi.org/10.5607/en22003","url":null,"abstract":"Patients suffering from rare human diseases often go through a painful journey for finding a definite molecular diagnosis prerequisite of appropriate cures. With a novel variant isolated from a single patient, determination of its pathogenicity to end such “diagnostic odyssey” requires multi-step processes involving experts in diverse areas of interest, including clinicians, bioinformaticians and research scientists. Recent efforts in building large-scale genomic databases and in silico prediction platforms have facilitated identification of potentially pathogenic variants causative of rare human diseases of a Mendelian basis. However, the functional significance of individual variants remains elusive in many cases, thus requiring incorporation of versatile and rapid model organism (MO)-based platforms for functional analyses. In this review, the current scope of rare disease research is briefly discussed. In addition, an overview of invertebrate MOs for their key features relevant to rare neurological diseases is provided, with the characteristics of two representative invertebrate MOs, Drosophila melanogaster and Caenorhabditis elegans, as well as the challenges against them. Finally, recently developed research networks integrating these MOs in collaborative research are portraited with an array of bioinformatical analyses embedded. A comprehensive survey of MO-based research activities provided in this review will help us to design a well-structured analysis of candidate genes or potentially pathogenic variants for their roles in rare neurological diseases in future.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 1","pages":"1 - 16"},"PeriodicalIF":2.4,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44528931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

Conformation-specific Antibodies Targeting Aggregated Forms of α-synuclein Block the Propagation of Synucleinopathy 靶向聚集型α-突触核蛋白的构象特异性抗体阻断突触核病的传播

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-02-28 DOI: 10.5607/en21039

Minsun Choi, Tae-kyung Kim, Jinhyung Ahn, Jun Sung Lee, Byung Chul Jung, Sungwon An, Dongin Kim, Min Jae Lee, I. Mook-Jung, S. H. Lee, Seung-Jae Lee

{"title":"Conformation-specific Antibodies Targeting Aggregated Forms of α-synuclein Block the Propagation of Synucleinopathy","authors":"Minsun Choi, Tae-kyung Kim, Jinhyung Ahn, Jun Sung Lee, Byung Chul Jung, Sungwon An, Dongin Kim, Min Jae Lee, I. Mook-Jung, S. H. Lee, Seung-Jae Lee","doi":"10.5607/en21039","DOIUrl":"https://doi.org/10.5607/en21039","url":null,"abstract":"Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 1","pages":"29 - 41"},"PeriodicalIF":2.4,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45571711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3

Interleukin 13 on Microglia is Neurotoxic in Lipopolysaccharide-injected Striatum in vivo 小胶质细胞上的白细胞介素13在体内对脂多糖注射纹状体具有神经毒性

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-02-28 DOI: 10.5607/en21032

Ah Reum Hong, Jae Geun Jang, Y. Chung, So-Yoon Won, Byung Kwan Jin

{"title":"Interleukin 13 on Microglia is Neurotoxic in Lipopolysaccharide-injected Striatum in vivo","authors":"Ah Reum Hong, Jae Geun Jang, Y. Chung, So-Yoon Won, Byung Kwan Jin","doi":"10.5607/en21032","DOIUrl":"https://doi.org/10.5607/en21032","url":null,"abstract":"To explore the potential function of interleukin-13 (IL-13), lipopolysaccharide (LPS) or PBS as a control was unilaterally microinjected into striatum of rat brain. Seven days after LPS injection, there was a significant loss of neurons and microglial activation in the striatum, visualized by immunohistochemical staining against neuronal nuclei (NeuN) and the OX-42 (complement receptor type 3, CR3), respectively. In parallel, IL-13 immunoreactivity was increased as early as 3 days and sustained up to 7 days post LPS injection, compared to PBS-injected control and detected exclusively within microglia. Moreover, GFAP immunostaining and blood brain barrier (BBB) permeability evaluation showed the loss of astrocytes and disruption of BBB, respectively. By contrast, treatment with IL-13 neutralizing antibody (IL-13NA) protects NeuN+ neurons against LPS-induced neurotoxicity in vivo. Accompanying neuroprotection, IL-13NA reduced loss of GFAP+ astrocytes and damage of BBB in LPS-injected striatum. Intriguingly, treatment with IL-13NA produced neurotrophic factors (NTFs) on survived astrocytes in LPS-injected rat striatum. Taken together, the present study suggests that LPS induces expression of IL-13 on microglia, which contributes to neurodegeneration via damage on astrocytes and BBB disruption in the striatum in vivo.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 1","pages":"42 - 53"},"PeriodicalIF":2.4,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45702244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

Diffusion MRI Connections in the Octopus Brain 章鱼大脑的扩散MRI连接

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-02-28 DOI: 10.5607/en21047

R. Jacobs

{"title":"Diffusion MRI Connections in the Octopus Brain","authors":"R. Jacobs","doi":"10.5607/en21047","DOIUrl":"https://doi.org/10.5607/en21047","url":null,"abstract":"Using high angle resolution diffusion magnetic resonance imaging (HARDI) with fiber tractography analysis we map out a meso-scale connectome of the Octopus bimaculoides brain. The brain of this cephalopod has a qualitatively different organization than that of vertebrates, yet it exhibits complex behavior, an elaborate sensory system and high cognitive abilities. Over the last 60 years wide ranging and detailed studies of octopus brain anatomy have been undertaken, including classical histological sectioning/staining, electron microscopy and neuronal tract tracing with injected dyes. These studies have elucidated many neuronal connections within and among anatomical structures. Diffusion MRI based tractography utilizes a qualitatively different method of tracing connections within the brain and offers facile three-dimensional images of anatomy and connections that can be quantitatively analyzed. Twenty-five separate lobes of the brain were segmented in the 3D MR images of each of three samples, including all five sub-structures in the vertical lobe. These parcellations were used to assay fiber tracings between lobes. The connectivity matrix constructed from diffusion MRI data was largely in agreement with that assembled from earlier studies. The one major difference was that connections between the vertical lobe and more basal supra-esophageal structures present in the literature were not found by MRI. In all, 92 connections between the 25 different lobes were noted by diffusion MRI: 53 between supra-esophageal lobes and 26 between the optic lobes and other structures. These represent the beginnings of a mesoscale connectome of the octopus brain.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 1","pages":"17 - 28"},"PeriodicalIF":2.4,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45028139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3

Alendronate Enhances Functional Recovery after Spinal Cord Injury 阿仑膦酸钠促进脊髓损伤后功能恢复

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-02-28 DOI: 10.5607/en21030

Yuna Choi, T. Shin

{"title":"Alendronate Enhances Functional Recovery after Spinal Cord Injury","authors":"Yuna Choi, T. Shin","doi":"10.5607/en21030","DOIUrl":"https://doi.org/10.5607/en21030","url":null,"abstract":"Spinal cord injury is a destructive disease characterized by motor/sensory dysfunction and severe inflammation. Alendronate is an anti-inflammatory molecule and may therefore be of benefit in the treatment of the inflammation associated with spinal cord injury. This study aimed to evaluate whether alendronate attenuates motor/sensory dysfunction and the inflammatory response in a thoracic spinal cord clip injury model. Alendronate was intraperitoneally administered at 1 mg/kg/day or 5 mg/kg/day from day (D) 0 to 28 post-injury (PI). The histopathological evaluation showed an alleviation of the inflammatory response, including the infiltration of inflammatory cells, and a decrease in gliosis. Alendronate also led to reductions in the levels of inflammation-related molecules, including mitogen-activated protein kinase, p53, pro-inflammatory cytokines, and pro-inflammatory mediators. Neuro-behavioral assessments, including the Basso, Beattie, and Bresnahan scale for locomotor function, the von Frey filament test, the hot plate test, and the cold stimulation test for sensory function, and the horizontal ladder test for sensorimotor function improved significantly in the alendronate-treated group at D28PI. Taken together, these results suggest that alendronate treatment can inhibit the inflammatory response in spinal cord injury thus improving functional responses.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 1","pages":"54 - 64"},"PeriodicalIF":2.4,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44145066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correlation between Alteration of Sharp-wave Ripple Coupled Cortical Oscillation and Long-term Memory Deficit in Alzheimer Disease Model Mice. 阿尔茨海默病模型小鼠锐波纹波耦合皮质振荡改变与长期记忆缺陷的关系

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21046

Hyunwoo Yang, Yong Jeong

{"title":"Correlation between Alteration of Sharp-wave Ripple Coupled Cortical Oscillation and Long-term Memory Deficit in Alzheimer Disease Model Mice.","authors":"Hyunwoo Yang, Yong Jeong","doi":"10.5607/en21046","DOIUrl":"https://doi.org/10.5607/en21046","url":null,"abstract":"Alzheimer's disease (AD) is the most common cause of dementia, characterized by prominent episodic memory dysfunction. Recent studies have suggested that there is a sequential mechanism in the memory deficit, with long-term ones preceding short-term ones. However, there is lack of explanation for these symptoms. Interaction between the hippocampus and retrosplenial cortex (RSC) during slow-wave sleep (SWS) is a crucial step for successful long-term memory formation. In particular, sharp-wave ripple (SWR) is a principal hippocampus oscillation that coordinates with RSC activity. To determine the relationship between memory dysfunction and SWR-related oscillation changes in AD, we implanted local field potential electrodes in the hippocampus and RSC of AD model mice (APP/PS1). We found that the SWR-coupled ripple wave increased in the RSC, while the amplitude of the SWR was preserved. In addition, the corresponding delta power in hippocampus and RSC was elevated, together with altered delta synchrony in AD mice. All these findings showed a significant correlation with long-term memory deficits measured in contextual fear conditions. Our study suggests that altered SWR-coupled oscillations are a possible underlying mechanism of episodic memory dysfunction in AD mice.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"430-440"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/27/en-30-6-430.PMC8752320.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Validation of the Thyrotoxicosis-associated Insomnia Model Induced by Thyroxine through Sympathetic Stimulation: Face, Construct and Predictive Perspectives. 甲状腺素通过交感神经刺激诱发甲状腺毒症相关失眠模型的验证:面部、结构和预测视角。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21023

Zhifu Ai, Hongwei He, Tingting Wang, Liling Chen, Chunhua Huang, Changlian Chen, Pengfei Xu, Genhua Zhu, Ming Yang, Yonggui Song, Dan Su

{"title":"Validation of the Thyrotoxicosis-associated Insomnia Model Induced by Thyroxine through Sympathetic Stimulation: Face, Construct and Predictive Perspectives.","authors":"Zhifu Ai, Hongwei He, Tingting Wang, Liling Chen, Chunhua Huang, Changlian Chen, Pengfei Xu, Genhua Zhu, Ming Yang, Yonggui Song, Dan Su","doi":"10.5607/en21023","DOIUrl":"https://doi.org/10.5607/en21023","url":null,"abstract":"Insomnia has become a common central nervous system disease. At present, the pathogenesis of insomnia is not clear. Animal models can help us understand the pathogenesis of the disease and can be used in transformational medicine. Therefore, it is very necessary to establish an appropriate model of insomnia. Clinical data show that insomnia patients with high levels of thyroxine and often accompanied by cardiovascular problems, a common mechanism underlying all of these physiological disruptions is the sympathetic nervous system. Combined with the characteristics of chronic onset of clinical insomnia, an insomnia model induced by long-term intraperitoneal injection of thyroid hormone has been created in our laboratory. In this paper, the insomnia-like state of the model was evaluated based on three validity criteria. Face validity has been demonstrated in metabolism, the Morris water maze, electrocardiogram (ECG) and electroencephalogram (EEG). Structure validity has been proved by the results of targeted metabolomics. After treatment with diazepam, a commonly used clinical anti-insomnia drug, the above physiological and pathological disorders were reversed. The results of comprehensive analysis show that the established thyrotoxicosis-associated insomnia model meets the validity requirement to establish an appropriate animal model of insomnia. The model presented in this article might help to study pathogenetic mechanisms of clinical insomnia, as well as to test promising methods of insomnia treatment.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"387-400"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/ed/en-30-6-387.PMC8752319.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Association between Changes in Cortical Thickness and Functional Connectivity in Male Patients with Alcohol-dependence. 男性酒精依赖患者皮质厚度变化与功能连通性的关系

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21036

Shin-Eui Park, Yeong-Jae Jeon, Hyeon-Man Baek

{"title":"Association between Changes in Cortical Thickness and Functional Connectivity in Male Patients with Alcohol-dependence.","authors":"Shin-Eui Park, Yeong-Jae Jeon, Hyeon-Man Baek","doi":"10.5607/en21036","DOIUrl":"https://doi.org/10.5607/en21036","url":null,"abstract":"Many studies have reported structural or functional brain changes in patients with alcohol-dependence (ADPs). However, there has been an insufficient number of studies that were able to identify functional changes along with structural abnormalities in ADPs. Since neuronal cell death can lead to abnormal brain function, a multimodal approach combined with structural and functional studies is necessary to understand definitive neural mechanisms. Here, we explored regional difference in cortical thickness and their impact on functional connection along with clinical relevance. Fifteen male ADPs who have been diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) underwent highresolution T1 and resting-state functional magnetic resonance imaging (MRI) scans together with 15 male healthy controls (HCs). The acquired MRI data were post-processed using the Computational Anatomy Toolbox (CAT 12) and CONN-fMRI functional connectivity (FC) toolbox with Statistical Parametric Mapping (SPM 12). When compared with male HCs, the male ADPs showed significantly reduced cortical thickness in the left postcentral gyrus (PoCG), an area responsible for altered resting-state FC patterns in male ADPs. Statistically higher FCs in PoCG-cerebellum (Cb) and lower FCs in PoCG-supplementary motor area (SMA) were observed in male ADPs. In particular, the FCs with PoCG-Cb positively correlated with alcohol use disorders identification test (AUDIT) scores in male ADPs. Our findings suggest that the association of brain structural abnormalities and FC changes could be a characteristic difference in male ADPs. These findings can be useful in understanding the neural mechanisms associated with anatomical, functional and clinical features of individuals with alcoholism.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"441-450"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d3/13/en-30-6-441.PMC8752324.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Chronic Restraint Stress Decreases the Excitability of Hypothalamic POMC Neuron and Increases Food Intake. 慢性约束应激降低下丘脑POMC神经元的兴奋性，增加食物摄入量。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21037

Go Eun Ha, Eunji Cheong

{"title":"Chronic Restraint Stress Decreases the Excitability of Hypothalamic POMC Neuron and Increases Food Intake.","authors":"Go Eun Ha, Eunji Cheong","doi":"10.5607/en21037","DOIUrl":"https://doi.org/10.5607/en21037","url":null,"abstract":"Stress activates the hypothalamic-pituitary-adrenal system, and induces the release of glucocorticoids, stress hormones, into circulation. Many studies have shown that stress affects feeding behavior, however, the underlying circuitry and molecular mechanisms are not fully understood. The balance between orexigenic (simulating appetite) and anorexigenic (loss of appetite) signals reciprocally modulate feeding behavior. It is suggested that proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus (ARC) of the hypothalamus are the first-order neurons that respond to the circulating signals of hunger and satiety. Here, we examined a chronic restraint stress model and observed an increase in food intake, which was not correlated with anhedonia. We investigated whether stress affects the properties of POMC and NPY neurons and found that chronic restraint stress reduced the excitatory inputs onto POMC neurons and increased the action potential threshold. Therefore, our study suggests that chronic stress modulates the intrinsic excitability and excitatory inputs in POMC neurons, leading to changes in feeding behavior.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"375-386"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/43/en-30-6-375.PMC8752322.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression. 齐墩果酸通过抑制miR-186-5p表达抑制缺血性脑卒中神经元焦亡。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21006

Shi-Chang Cai, Xiu-Ping Li, Xing Li, Gen-Yun Tang, Li-Ming Yi, Xiang-Shang Hu

{"title":"Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression.","authors":"Shi-Chang Cai, Xiu-Ping Li, Xing Li, Gen-Yun Tang, Li-Ming Yi, Xiang-Shang Hu","doi":"10.5607/en21006","DOIUrl":"https://doi.org/10.5607/en21006","url":null,"abstract":"Ischaemic stroke is a common condition leading to human disability and death. Previous studies have shown that oleanolic acid (OA) ameliorates oxidative injury and cerebral ischaemic damage, and miR-186-5p is verified to be elevated in serum from ischaemic stroke patients. Herein, we investigated whether OA regulates miR-186-5p expression to control neuroglobin (Ngb) levels, thereby inhibiting neuronal pyroptosis in ischaemic stroke. Three concentrations of OA (0.5, 2, or 8 μM) were added to primary hippocampal neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R), a cell model of ischaemic stroke. We found that OA treatment markedly inhibited pyroptosis. qRT-PCR and western blot revealed that OA suppressed the expression of pyroptosis-associated genes. Furthermore, OA inhibited LDH and proinflammatory cytokine release. In addition, miR-186-5p was downregulated while Ngb was upregulated in OA-treated OGD/R neurons. MiR-186-5p knockdown repressed OGD/R-induced pyroptosis and suppressed LDH and inflammatory cytokine release. In addition, a dual luciferase reporter assay confirmed that miR-186-5p directly targeted Ngb. OA reduced miR-186-5p to regulate Ngb levels, thereby inhibiting pyroptosis in both OGD/R-treated neurons and MCAO mice. In conclusion, OA alleviates pyroptosis in vivo and in vitro by downregulating miR-186-5p and upregulating Ngb expression, which provides a novel theoretical basis illustrating that OA can be considered a drug for ischaemic stroke.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"401-414"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/0e/en-30-6-401.PMC8752321.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2