检索结果-南通市图书馆

Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson's disease

Neural Regeneration Research 2023年第8期18卷 1818-1826页

作者： Hai-Yang Yu Tong Sun Zhen Wang Hong Li Duo Xu Jing An Lu-Lu Wen Jia-Yi Li Wen Li Juan Feng Department of Neurology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Laboratory of Research in Parkinson’s Disease and Related Disorders Health Sciences InstituteChina Medical UniversityShenyangLiaoning ProvinceChina Neural Plasticity and Repair Unit Department of Experimental Medical ScienceLund UniversityLundSweden

Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.

关键词： diabetes mellitus dipeptidyl peptidase 4 inhibitor exendin-4 glucagon-like peptide-1 receptor agonist 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine linagliptin microglia neuroinflammation NLRP3 inflammasome Parkinson's disease pyroptosis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

MADOPAR-INDUCED DYSKINESIA IN 1-METHYL-4-PHENYL-1,2,3,6-tetrahydropyridine (MPTP) HEMIPARKINSONIAN MONKEY MODEL

引用

Medical Bulletin of Shanghai Jiaotong University 1991年第1期14卷 41-46页

作者：陈生弟周孝达钱可久徐德隆唐琴梅徐修蓉 Department of Neurology Renji Hospital SSMU Shanghai Department of Neurology Ruijin Hospital SSMU Shanghai Shanghai Institute of Materia Medica Academia Sinica Shanghai

Infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the right common carotid artery produced hemiparkinsonian syndrome on contralateral limbs in 5 rhesus monkeys. The hemiparkinsonian syndrome produced responded to madopar medication and the circling motion changed from toward the MPTP-treated side to away from the MPTP-treated side. Long term use of madopar developed a peak-dose dyskinesia of the face and limbs at the contralateral side. The toxic effect of MPTP was confirmed biochemically by reduction of nigrostriatal DA and histologically by degeneration of nigral neurons on the MPTP-treated side. It is concluded that this hemiparkinsonian monkey model will be of value in the elucidation of the neural mechanism underlying L-DOPA or DA agonists induced dyskinesia in Parkinson’s disease and in the search for newer methods of treatment which would produce less dyskinesia.

关键词： dyskinesia madopar hemiparkinsonism rhesus monkey 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine (MPTP)

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics approach

引用

Journal of Traditional Chinese Medicine 2021年第3期41卷 390-396页

作者： Joong Sun Kim Hye-Sun Lim Byeong Cheol Moon Mary Jasmin Ang Sung-Ho Kim Changjong Moon Boseok Seong Yunji Jang Hyung-Yong Kim Chul Kim Herbal Medicine Resources Research Center Korea Institute of Oriental MedicineJeollanamdo 58245Republic of Korea College of Veterinary Medicine and BK21 Plus Project Team Chonnam National UniversityGwangju 61186Republic of Korea Future Medicine Division Korea Institute of Oriental MedicineDaejeon 34054Republic of Korea Research and Development Center Insilicogen Inc.Yonginsi 16954Republic of Korea

OBJECTIVE: To investigate whether scorpion extract elicits a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated mice models, and the genes associated with the therapeutic effects using RNA sequencing(seq)analysis.METHODS: This study investigated the changes in interaction between messenger ribonucleic acid(m RNA) expression and deoxyribonucleic acid(DNA) methylation related to the protective effects of scorpion extracts, in the substantia nigra(SN)region of a MPTP-induced Parkinson's disease(PD)model.RESULTS: In this model, scorpion extracts attenuated the motor impairment as demonstrated by the rotarod and open field tests. Scorpion extracts consistently attenuated the decrease of tyrosine hydroxylase(TH) positive neural cells in the SN and striatum of mice. We profiled genomewide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated MPTP-induced PD mice and scorpion extracttreated MPTP-induced PD mice. In total, 13 479 differentially expressed genes were identified in association with the anti-PD effect of the scorpion extract, mainly in the promoter and coding regions.Among them, 47 were negatively correlated downregulated genes. Nineteen genes out of 47 downregulated genes were negatively correlated with the expression of the other 28 genes. Among these genes, SGSM1 was related to dopaminergic neurons including dopamine transporters, TH, dihydroxyphenylalanine decarboxylase, and dopamine D2 receptor.CONCLUSION: This study provides insights into the anti-parkinsonian effects of scorpion extract and reveals the epigenetic targets in its therapeutic mechanism.

关键词： scorpions 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine Parkinson disease DNA methylation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Prenatal and Postnatal Exposures to 1-Methyl-4-phenyl-1,2,3,6-tetra Hydropyridine (MPTP) Impaired Mouse Midbrain Dopamine System and May Produce a Predisposing and Inducing Model for Parkinson’s Disease

引用

Journal of Behavioral and Brain Science 2012年第4期2卷 485-494页

作者： Gladson Muthian Jennifer King Lemuel Dent Marquitta Smith Veronica Mackey Clivel Charlton Department of Neuroscience and Pharmacology Meharry Medical College Nashville USA

Dopamine cell bodies in the substantia nigra of the midbrain and with their terminals projecting to the neostriatum form the nigrostriatum and these dopamine neurons degenerate in Parkinson’s disease (PD). Based on metabolic and func- tional specialization of the cell bodies versus the axon terminals, the level and disposition of dopamine, its metabolites and enzymes are different in both regions and are likely to be affected differently in PD. We examined changes in the midbrain dopamine system following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to test the hypothesis that a predisposing/sensitization stage and a inducing/precipitating stage underlie PD. Pregnant mice were treated with a low dose of MPTP during gestation days 8 - 12 to model the predisposing/sensitization stage, by interrupting the fetal mid- brain dopamine system during its neurogenesis. For the inducing/precipitating stage, the 12-weeks offspring were ad- ministered MPTP. The prenatal-MPTP offspring appear normal, but midbrain dopamine, 3,4-di-hydroxy-phenyl-acetic- acid, 3-methoxytyramine, tyrosine-hydroxylase and L-aromatic-amino-acid-decarboxylase, were reduced by 49.6%, 48%, 54%, 20.9% and 25%. Postnatal-MPTP of 10, 20, 30 mg/kg administered to the prenatal-PBS vs prenatal-MPTP offspring reduced midbrain dopamine by 43.6%, 47.2%, 70.3% vs 85.4%, 89.1%, 95.2%;tyrosine-hydroxylase by 30%, 63%, 81% vs 30.7%, 70.4%, 91.4%;L-aromatic-amino-acid-decarboxylase by 0%, 2%, 40% vs 32%, 40%, 58%. The prenatal-MPTP may render the DA system sensitive by causing sub-threshold reduction of DA, its metabolites and en- zymes, enabling postnatal-MPTP to reduce dopamine above the 70% - 80% PD-inducing threshold. Thus, the study may produce a prenatal predisposing/sensitization and postnatal inducing/precipitation model of PD. It also indicates that some cases of PD may have a fetal basis, in which sub-threshold nigrostriatal impairments occur early in life and PD-symptoms are induced during aging by further insults to the dopaminergic system that

关键词： Parkinson’s Disease Midbrain 1-Methyl-4-Phenyl-1 2 3 6-tetrahydropyridine (MPTP) Dopamine Tyrosine Hydroxylase L-aromatic Amino Acid Decarboxylase Sensitization Precipitation

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：