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| 1 | Local transgene expression and whole-body transgenesis to model brain diseases in nonhuman primate显示文摘Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector-mediated transgene delivery and the new genome-editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate. | Lucie Chansel-Debordeaux Erwan Bezard | 2019 | Animal Models and Experimental Medicine2019，2，1： | 3 |
| 2 | 茶多酚对6-OHDA诱导的SH-SY5Y细胞凋亡的保护作用显示文摘茶多酚在体内具有广泛的生物活性和药理作用,有助于预防与氧化应激相关的疾病,比如癌症,心血管疾病,神经退行性疾病和衰老.氧化应激参与了帕金森病(PD)的病理进程.活性氧在PD的发病机制中发挥了重要的作用,氧自由基直接损伤细胞膜引起脂质过氧化,损伤蛋白质和各种功能酶引起蛋白质沉淀,诱导促凋亡因子的表达,损伤DNA,最终导致了细胞的凋亡.然而,关于茶多酚对PD的预防和治疗作用目前还不清楚.本文应用氧化应激诱导的PD病理细胞模型,评价了茶多酚的神经保护作用.结果表明茶多酚这类植物天然抗氧化剂对氧化应激诱导的细胞凋亡具有明确的抑制作用.实验中我们选择了6-OHDA诱导的SH-SY5Y细胞作为细胞模型,运用了MTT、流式细胞术、荧光显微成相,竞争性ELISA和蛋白质杂交等方法研究了SH-SY5Y细胞的凋亡特性.结果表明,6-OHDA对SH-SY5Y有时间-浓度依赖性细胞毒性,100μmol/L6-OHDA处理24 h,细胞活力减少50%,同时伴随着活性氧增加(用ESR),线粒体膜电位降低,细胞内钙离子和一氧化氮增加,nNOS和iNOS表达量上升及蛋白结合的硝基酪氨酸水平升高.单独茶多酚处理对细胞没有太大的影响,而茶多酚预处理可显著降低6-OHDA所产生的细胞毒性.溶液实验证明,茶多酚对6-OHDA的自氧化有浓度-时间依赖性抑制作用(用ESR).本研究表明茶多酚可能是通过活性氧-一氧化氮途径,减少过氧亚硝基的生成来对6-OHDA诱导的细胞凋亡表现保护作用的.本文的实验结果提示茶多酚在治疗PD等慢性神经退行性疾病上可能是一种有着潜在疗效的药物. | 郭树红 BEZARD Erwan 赵保路 | 2006 | 波谱学杂志2006，23，4： | 2 |
| 3 | Microdialysis in awake macaque monkeys for central nervous system pharmacokinetics显示文摘Background: The brain bioavailability of novel small molecules developed to address central nervous system disease is classically documented through ex vivo or in vivo analyses conducted in rodent models. Data acquired in rodent models are, however,not easily transferrable to human as the pharmacokinetic and pharmacodynamics profiles of the species are quite different.Methods: Using drugs selected for their differential transport across the blood-brain barrier, we here demonstrate the feasibility of brain microdialysis in normal vigil macaque monkey by measuring brain extracellular fluid bioavailability of carbamazepine, digoxin, oxycodone, and quinidine.Results: All drugs, but digoxin, were found in dialysate samples. Drugs that are substrate of P-glycoprotein show a difference of bioavailability or brain pharmacokinetic parameters between rodents and primates.Conclusion: Data suggest that brain microdialysis in vigil macaque monkey, the species of choice for classic pharmacokinetic/pharmacodynamics studies could help predicting human brain bioavailability of a small molecule depending on the protein involved in the efflux transport from the brain. | Thibaud Thiollier Caisheng Wu Gregory Porras Erwan Bezard Qin Li Jinlan Zhang Hugues Contamin | 2018 | Animal Models and Experimental Medicine2018，1，4： | 2 |
| 4 | Priming for 1-dopa-induced dyskinesia in Parkinson's disease: a feature inherent to the treatment or the disease显示文摘 | Nadjar A Gerfen CR Bezard E | 2009 | Prog Neurobiol2009，87，： | 1 |
| 5 | Purification and antigenic analysis of the major 25-kilodalton outer membrane protein of Brucella abortus显示文摘 | CLOECKAERT A ZYGMUNT M S BEZARD G | 1996 | Res Microbiol1996，147，4： | 1 |
| 6 | Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS-NO pathway显示文摘 | Guo S Bezard E Zhao B | 2005 | Free Radie Biol Med2005，39，5： | 1 |
| 7 | Partial synthesis of major human metabolites of docetaxel 显示文摘 | Commercon A Bourzat JD Bezard D | 1994 | Tetrahedron1994，50，10： | 1 |
| 8 | Effects of different schedules of MPTP administration on dopaminergic neurodegeneration in mice 显示文摘 | Bezard E Dovero S Bioulac B | 1997 | Exp Neurol1997，148，： | 1 |
| 9 | Protective Effects of Green Tea Polyphenols in the 6-OHDA Rat Model of Parkinson’s Disease Through Inhibition of ROS-NO Pathway显示文摘 | Shuhong Guo Jingqi Yan Tangbin Yang Xianqiang Yang Erwan Bezard Baolu Zhao | 2007 | Biological Psychiatry2007，，12： | 1 |
| 10 | Comparison of eight clinical rating scales used for the assessment of MPTP-induced parkinsonism in the Macaque monkey显示文摘 | Imbert C Bezard E Guitraud S | 2000 | J Neurosci Methods2000，96，1： | 1 |
| 11 | Pathophysiology of levodopa induced dyskinesia: potential for new therapies 显示文摘 | Bezard E Brotchie JM Gross CE | 2001 | Nat Rev Neurosci2001，2，： | 1 |
| 12 | A tale on animal models of Parkinson's disease 显示文摘 | Bezard E Przedborski S | 2011 | Mov Disord2011，26，6： | 1 |
| 13 | Noradrenergic modulation of subthalamie nucleus activity: behavioral and electrophysiologieal evidence in intact and 6-hydroxydopamine- lesioned rats 显示文摘 | Belujon P Bezard E Taupignon A | 2007 | J Neurosci2007，27，36： | 1 |
| 14 | Purification and antigenic analysis of the major 25-kilodalton outer membrane protein of Brucella abortus 显示文摘 | Cloeckaert A Zygmunt MS Bezard G | 1996 | Res Microbiol1996，147，4： | 1 |
| 15 | Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter 显示文摘 | Bezard E Gross CE Fournier MC | 1999 | Exp Neurol1999，155，： | 1 |
| 16 | A tale on animal models of Parkinson disease 显示文摘 | Bezard E Przedborski S | 2011 | Mov Disord2011，26，6： | 1 |
| 17 | Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS-NO pathway显示文摘 | Guo S Bezard E Zhao B | 2005 | Free Radic Biol Med2005，39，5： | 1 |
| 18 | Effect of the alpha 2 adrenoreceptor antagonist, idazoxan, on motor disabilities in MPTP- treated monkey 显示文摘 | Bezard E Brefel E Tisou F | 1999 | Prog Neuropsychopharmacol Biol Psychiatry1999，23，7： | 1 |
| 19 | Systemic gene delivery to the central nervous system using Adeno-associated virus显示文摘 | Bourdenx M Dutheil N Bezard E | 2014 | Front Mol Neurosci2014，7，： | 1 |
| 20 | Cortical stimulation and epileptic seizure:a study of the potential risk in primates显示文摘 | Bezard E Boraud T Nguyen JP | 1999 | Neurosurgery1999，45，2： | 1 |
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