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Wnt3a protects SH-SY5Y cells against 6-hydroxydopamine toxicity by restoration of mitochondria function

Translational Neurodegeneration 2015年第1期4卷 76-83页

作者： Lei Wei Li Ding Ming-shu Mo Ming Lei Limin Zhang Kang Chen pingyi xu Department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Neurology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of pathology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Division of Clinical Laboratory Zhongshan Hospital of Sun Yat-sen UniversityZhongshan 528403China

Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine(6-OHDA).Methods:Wnt3a-conditioned medium(Wnt3a-CM)was used to intervene dopaminegic SH-SY5Y cells treated with *** toxicity was determined by cell viability and lactate dehydrogenase leakage(LDH)*** mitochondria function was measured by the mitochondrial membrane potential,while oxidative stress was monitored with intracellular reactive oxygen species(ROS).Western blot analysis was used to detect the expression of GSK3β,β-catenin as well as ***:Our results showed that 100μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential,reduced the level ofβ-catenin and p-Akt,increased LDH leakage,ROS production and the ratio of p-GSK3β(Tyr216)to p-GSK3β(Ser9).However,Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these ***:Activating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly,which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.

关键词： Wnt3a 6-OHDA Mitochondria function Parkinson’s disease

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Features on N/P ratio of plants with different functional groups between two types of steppe in semi-arid area

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Research in Cold and Arid Regions 2019年第5期11卷 371-381页

作者： YueDan Zhao XingDong He Lei Chen XinFeng Ding MengQi Li pingyi xu YuBao Gao College of Life Sciences Nankai University

The differences in nitrogen/phosphorus(N/P)ratios of different functional groups in ecology are more helpful in explaining species competition and community *** on the functional groups of plant growth type,carbon metabolism pathway,root type and phylogenetic type,we analyzed characteristics of leaf N/P ratios of 77 species in Sanggendalai(typical grassland zone)of Zhenglan Banner,Inner Mongolia,China and 91 species in the Habahu National Nature Reserve(desertified grassland zone)in Yanchi County of Ningxia,*** results show that the N/P ratio(16.91)of C3 plants in the desertified steppe was significantly larger than that(12.72)in the typical steppe,but there was no significant difference between the N/P ratios of C4 plants in the two *** was no significant difference in N/P ratios between C3 plants and C4 plants in the same ***,the N/P ratio(16.60)of dicotyledons in desertified steppe were significantly higher than that(12.98)in typical steppe,while differences in N/P ratios between monocotyledonous plants of the two zones was not significant,and there existed no significant difference in N/P ratios between dicotyledonous and monocotyledonous plants in the same *** N/P ratio had significant difference between gramineous and non-gramineous plants in the typical steppe but not in the desertified steppe,but there existed no significant difference in N/P ratios among different root types of perennial herbaceous plants in the same type of steppe or between two types of ***,different features on the N/P ratios of C3 plants and dicotyledonous plants between typical steppe and desertified steppe may lead to different growth status of plants,and the N/P ratio stoichiometric of the same plant functional group may be a foundation of the changes of a plant community.

关键词： semi-arid region plant N/P ratio plant functional groups desertified steppe typical steppe

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The biomarkers of immune dysregulation and inflammation response in Parkinson disease

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Translational Neurodegeneration 2016年第1期5卷 131-136页

作者： Li Chen Mingshu Mo Guangning Li Luan Cen Lei Wei Yousheng Xiao Xiang Chen Shaomin Li Xinling Yang Shaogang Qu pingyi xu Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangdong 510120China Department of Neurology The First Affiliated Hospital of Sun Yat-sen UniversityGuangdong 510080China Department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangdong 510082China Ann Romney Center for Neurologic Disease Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Department of Neurology The Third Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830011China Department of Blood Transfusion The Fifth Affiliated HospitalSouthern Medical UniversityGuangzhouGuangdong 510900China Department of Neurology The Affiliated Huadu Hospital of Southern Medical UniversityGuangzhou 510800China

Parkinson’s disease(PD)is referring to the multi-systemicα-synucleinopathy with Lewy bodies deposited in *** ageing,the environmental and genetic factors work together and overactive major histocompatibility complex pathway to regulate immune reactions in central nerve system which resulting in neural degeneration,especially in dopaminergic *** a series of biomarkers,the human leukocyte antigen genes with its related proteomics play cortical roles on the antigen presentation of major histocompatibility complex molecules to stimulate the differentiation of T lymphocytes and i-proteasome activities under their immune response to the PD-related environmental alteration and genetic ***,dopaminergic drugs change the biological characteristic of T lymphatic cells,affect theα-synuclein presentation pathway,and inhibit T lymphatic cells to release cytotoxicity in PD *** together,the serum inflammatory factors and blood T cells are involved in the immune dysregulation of PD and inspected as the potential clinic biomarkers for PD prediction.

关键词： Parkinson’s disease α-synucleinopathy Inflammation Biomarkers

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Mesenchymal stem cells inactivate microglia in peri-infarct through CD200-CD200R pathway in stroke rats

Mesenchymal stem cells inactivate microglia in peri-infarct ...

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中国神经科学学会第十二届全国学术会议

作者： Zhihua yang xueli Cai Shaoming Li pingyi xu Department of neurology the first affiliated hospital of Guangzhou Medical University

Back group/Objectives: The effects of neuroimmune modulation of BM-MSCs transplantation for stroke by inactivating microglia were proved in some study, but the related mechanism and the time window of the immunomodulation is not clear. Whether BM-MSCs can carry the effect in the acute stage of stroke, whether CD200-CD200 R pathway is involved in the immunomodulation after BM-MSCs transplantation. It is the aim of our study. Method: MCAO（Middle Cerebral Artery Occlusion） rat model was used to evaluate the therapeutic efficacy of BM-MSCs（Bone Marrow-Marrow Stromal Cell） on acute stage of ischemic stroke rats. Activated microglia were evaluated by IBA-1 ***200-CD200 R pathway related mechanism were explored by peri-infarct injection of CD200 R antibody. The effects transplantation on the changes of IBA-1 and CD200 expression were determined by the western blot. Neuronal CD200 coexpression in peri-infarct and BM-MSCs CD200 co-expression were detected by double fluorescence. Neuronal damage was evaluated by Neu N immunobiological stain, Tunel stain and CV stain（Crystal Violet） in the peri-infarct and in ***: Transplanted BM-MSCs can have neuroimmune modulation by inactivate the microglia in peri-infarct by IBA-1 immunoflurences and western blot analysis and partially reversed by CD200 R antibody in the peri-infarct areas. BM-MSCs could migrate to the infarct area, but not in CA1. The control group had a significantly higher infarct zone percentage than that of the transplanted groups. These results suggest that transplanted BM-MSCs can migrate into the peri-infarct zone and significantly reduce the volume of the infarct zone. There were more Neu N and CV positive cells in CA1 and peri-infarct in transplantation group than cell numbers in the same areas in the control group. There were also less Tunnel positive cells in CA1 and in peri-infarct areas in transplant group than in control group. There were more Neuronal CD200 expression and CD200 exp

关键词： Mesenchymal stem cells Microglia Stroke CD200

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Peripheral Lymphocyte Subsets as a Marker of Parkinson's Disease in a Chinese Population

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Neuroscience Bulletin 2017年第5期33卷 493-500页

作者： Luan Cen Chaohao Yang Shuxuan Huang Miaomiao Zhou Xiaolu Tang Kaiping Li Wenyuan Guo Zhuohua Wu Mingshu Mo Yousheng Xiao Xiang Chen Xinling Yang Qinhui Huang Chaojun Chen Shaogang Qu pingyi xu Department of Neurology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Department of Neurology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510080China State Key Laboratory of Respiratory Disease The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Neurology The Second Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830011China Department of Neurology Guangzhou Chinese MedicalIntegrated Hospital(Huadu)Guangzhou 510800China Clinical Medicine Research Centre Shunde Hospital of Southern Medical UniversityFoshan 528300China

In this study, we conducted a clinical analysis of lymphocyte subtypes in 268 patients with Parkinson＇s disease （PD） to assess their clinical impact as a potential marker of advanced PD in Chinese patients. The participants comprised 268 sporadic PD patients and 268 healthy controls. The numbers of natural killer （NK） cells and CD3＋, CD3＋CD4＋, CD3＋CD8＋, and CD19＋ lympho- cytes from peripheral blood were determined by immunos- taining and flow cytometric analysis and the percentages of these CD＋ T cells were calculated. The ratio of regulatory T （Treg）/helper T 17 （Thl7） lymphocytes from 64 PD patients and 46 controls was determined by flow cytometric analysis. The results showed that the percentage of NK cells was higher in advanced PD patients than in controls （22.92% ± 10.08% versus 19.76% ±10.09%, P= 0.006）, while CD3＋ T cells are decreased （62.93% ±9.27% versus 65.75% ± 9.13%, P = 0.005）. The percentage of CD19＋ B cells in male patients was lower （P = 0.021） than in female patients, whereas NK cells were increased （P 〈 0.0001）. The scores on the Unified Parkinson＇s Disease Rating Scale （UPDRS） and the Non-Motor Symptoms Scale in late-onset PD patients were significantly higher than those in earlyonset patients （P = 0.024 and P = 0.007, respectively）. The percentage of CD19＋ B cells in patients with UPDRS scores 〉24 was lower than in those with scores 〈24 （10.17% ± 4.19% versus 12.22% ± 5.39%, P = 0.009）. In addition, the Treg/Th17 ratio in female patients was higher than that in female controls （13.88 ± 6.32 versus 9.94 ±4.06, P = 0.042）. These results suggest that the percentages of NK cells, CD3＋ T cells, and CD19＋ B cells along with the Treg/Th17 ratio in peripheral blood may be used to predict the risk of PD in Chinese individuals and provide fresh avenues for novel diagnostic biomarkers and therapeutic designs.

关键词： Parkinson's disease · Biological marker ·Lymphatic cell

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CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

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Neural Regeneration Research 2024年第1期19卷 196-204页

作者： Xiang Chen Yuwan Lin Zhiling Zhang Yuting Tang Panghai Ye Wei Dai Wenlong Zhang Hanqun Liu Guoyou Peng Shuxuan Huang Jiewen Qiu Wenyuan Guo Xiaoqin Zhu Zhuohua Wu Yaoyun Kuang pingyi xu Miaomiao Zhou Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology The People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's ***-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy ***,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea ***,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of *** found that CHCHD2 protected mitochondria from developing MPP^(+)-induced *** normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase *** addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and *** weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this *** findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

关键词： ATP synthase(F1F0-ATPase) coiled-coil helix coiled-coil helix domain containing 2 dopaminergic neuron mitochondrial dysfunction neurodegeneration oligomycin sensitivity-conferring protein Parkinson's disease T61I mutation tyrosine hydroxylase

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Microglial brain-derived neurotrophic factor regulates neurogenesis in epilepsy

Microglial brain-derived neurotrophic factor regulates neuro...

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中国神经科学学会第十二届全国学术会议

作者： Mingshu Mo Ukpong B.Eyo Jiyun Peng pingyi xu Long-Jun Wu Department of Neurology First Affiliated Hospital of Guangzhou Medical University Department of Cell Biology and Neuroscience Rutgers University Deparment of Neurology Mayo Clinic

The microglia activation, neurogenesis and mossy sprouting fiber（MSF） in dentate gyrus（DG） increase after epilepsy. Recent studies showed that microglia regulate synaptic pruning and release brain-derived neurotrophic factor（BDNF） to promote synapse formation in brain development. However, the interaction between microglia and neurogenesis, MSF after epilepsy in adult remains unclear. To address this question, we used CX3CR1 Cre ER/+:R26 i DTR/+ mice for microglia conditional ablation. With these mice, we can induce diphtheria toxin（DT） receptors on microglia by tomoxifen and deplete the microglia by DT injection. Using kainic acid（KA） induced epilepsy model, we confirmed that the number of doublecortin（DCX）, DCX+/Ki67+, DCX+/Brdu+ cells in DG and their sprouting fiber projected to CA3 increased significantly, as well as microglia activation in granular layers. After microglia ablation, the increased DCX+ cells and their sprouting fiber in epilepsy were dramatically inhibited. Furthermore, using CX3CR1 Cre ER/+:BDNFfl/fl mice for conditional manipulation of BDNF expression from microglia, we found that the increase of DCX+, DCX+/Ki67+, DCX+/Brdu+ and their sprouting fiber in epilepsy were also significantly inhibited. Our study suggested that BDNF released form microglia promotes the neurogenesis after epilepsy.

关键词： Brain-derived neurotrophic factor Microglia Neurogenesis Epilepsy

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Chaperone-mediated Autophagy Regulates Cell Growth by Targeting SMAD3 in Glioma

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Neuroscience Bulletin 2022年第6期38卷 637-651页

作者： Hanqun Liu Yuxuan Yong Xingjian Li Panghai Ye Kai Tao Guoyou Peng Mingshu Mo Wenyuan Guo Xiang Chen Yangfu Luo Yuwan Lin Jiewen Qiu Ziling Zhang Liuyan Ding Miaomiao Zhou Xinling Yang Lin Lu Qian Yang pingyi xu Department of Neurology The First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Neurosurgery Tangdu HospitalThe Fourth Military Medical UniversityXi'an 710038China Department of Neurology The Second Affliated Hospital of Xinjiang Medical UniversityUrimqi 830054China Department of Experiment Surgery Tangdu HospitalThe Fourth Military Medical UniversityXi'an 710038China

Previous studies suggest that the reduction of SMAD3(mothers against decapentaplegic homolog 3)has a great impact on tumor development,but its exact pathological function remains *** this study,we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues,in which LAMP2A(lysosome-associated membrane protein type 2A)was significantly ***2A is a key ratelimiting protein of chaperone-mediated autophagy(CMA),a lysosome pathway of protein degradation that is activated in *** carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ,which has been proposed to be a targeting sequence for *** vitro,we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition,which was regulated by LAMP2A and interacted with HSC70(heat shock cognate 71 kDa protein).Using isolated lysosomes,amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process,which affected the CMA pathway in which SMAD3 was ***,down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and *** together,these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of ***,targeting the SMAD3-LAMP2Amediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

关键词： Glioma-SMAD3 Chaperone-mediated autophagy Cell growth

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阿司匹林对阿尔茨海默病患者脑脊液中细胞因子表达的影响

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中国综合临床 2007年第9期23卷 799-800页

作者：高强徐评议南海西部石油公司职工医院神经科广东省湛江市524057 中山大学附属第一医院神经科

目的探讨阿尔茨海默病(Alzheimer's disease,AD)患者脑脊液中白细胞介素-15(IL-15)、生长转化因子β_1(TGF-β_1)的表达情况及阿司匹林对白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、IL-15和TGF-β_1的影响。方法应用ELISA反应体系... 详细信息

目的探讨阿尔茨海默病(Alzheimer's disease,AD)患者脑脊液中白细胞介素-15(IL-15)、生长转化因子β_1(TGF-β_1)的表达情况及阿司匹林对白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、IL-15和TGF-β_1的影响。方法应用ELISA反应体系分别检测AD患者使用阿司匹林前后及对照组脑脊液中的IL- 6、IL-15、TGF-β_1和TNF-α表达的水平。结果①AD患者IL-15、TGF-β_1表达明显升高,与对照组比较均有统计学意义(均P<0.01);②阿司匹林可以降低脑脊液中IL-6、IL-15、TGF-β_1、TNF-α水平,与治疗前比较均有统计学意义(均P<0.05)。结论IL-15、TGF-β_1参与AD疾病的发生过程;阿司匹林可能通过抑制炎性细胞因子分泌而对AD患者发挥治疗作用。

关键词：阿尔茨海默病阿司匹林细胞因子

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CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson’s disease

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Chinese Medical Journal 2022年第13期135卷 1588-1596页

作者： Lin Lu Hengxu Mao Miaomiao Zhou Yuwan Lin Wei Dai Jiewen Qiu Yousheng Xiao Mingshu Mo Xiaoqin Zhu Zhuohua Wu Zhong Pei Wenyuan Guo pingyi xu Xiang Chen Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510120China Department of Neurology The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhouGuangdong 511436China Department of Neurology National Key Clinical Department and Key Discipline of NeurologyThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China.

Background:Parkinson’s disease(PD)is the second most common neurodegenerative disease after Alzheimer’s *** dysfunction is involved in the pathology of ***-coil-helix-coiled-coil-helix domain-containing 2(CHCHD2)was identified as associated with autosomal dominant ***,the mechanism of CHCHD2 in PD remains ***:Short hairpin RNA(ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma(SHSY5Y)and HeLa ***-native polyacrylamide gel electrophoresis(PAGE)and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system(MICOS).Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and *** injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)administration were used to examine the influence of CHCHD2 in ***:We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium(MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse ***,we identified that CHCHD2 interacted with Mic10,and overexpression of CHCHD2 can protect against MPP+-induced MICOS impairment,while knockdown of CHCHD2 impaired the stability of ***:This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex,which contributes to protecting mitochondrial function in PD.

关键词： CHCHD2 MICOS complex Mic10 Parkinson’s disease

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