Objective To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic （DAergic） neurons for Parkinson＇s disease （PD） research and to determine the effect of differentiation on this ...Objective To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic （DAergic） neurons for Parkinson＇s disease （PD） research and to determine the effect of differentiation on this cell model. Date sources The data of this review were selected from the original reports and reviews related to SH-SY5Y cells published in Chinese and foreign journals （Pubmed 1973 to 2009）. Study selection After searching the literature, 60 articles were selected to address this review. Results The SH-SY5Y cell line has become a popular cell model for PD research because this cell line posses many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-13-hydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained. However, different differentiating agents induce different neuronal phenotypes and biochemical changes. For example, retinoic acid induces differentiation toward a cholinergic neuronal phenotype and increases the susceptibility of SH-SY5Y cells to neurotoxins and neuroprotective agents, whereas treatment with retinoic acid followed by phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in a DAergic neuronal phenotype and decreases the susceptibility of cells to neurotoxins and neuroprotective agents. Some differentiating agents also alter kinetics of 1-methyl-4-phenyl-pyridinium （MPP~） uptake, making SH-SY5Y cells more similar to primary mesencephalic neurons. Conclusions Differentiated and undifferentiated SH-SY5Y cells have been widely used as a cell model of DAergic neurons for PD research. Some differentiating agents afford SH-SY5Y cells with more potential for studying neurotoxiclty and neuroprotection and are thus more relevant to experimental PD research.展开更多
Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be ...Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites 展开更多
目的:通过鱼藤酮持续灌胃构建的帕金森病小鼠模型研究α-突触核蛋白寡聚体(α-Syn)的毒性作用机制。方法:48只老年雄性C57小鼠随机分为鱼藤酮组和对照组,每组24只,鱼藤酮组灌注0.01 mL/g鱼藤酮氯仿溶液,对照组灌注0.01 m L/g氯仿溶液,...目的:通过鱼藤酮持续灌胃构建的帕金森病小鼠模型研究α-突触核蛋白寡聚体(α-Syn)的毒性作用机制。方法:48只老年雄性C57小鼠随机分为鱼藤酮组和对照组,每组24只,鱼藤酮组灌注0.01 mL/g鱼藤酮氯仿溶液,对照组灌注0.01 m L/g氯仿溶液,均连续灌胃12周。于灌胃后取脑,行蛋白质印迹实验检测α-Syn表达水平、透射电镜观察中脑黑质神经元超微结构;于灌胃前、后取脑,免疫组化染色观察黑质部位酪氨酸羟化酶(TH)阳性细胞密度,并检测脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)和丙二醛(MDA)水平。结果:灌胃12周后,Western blot显示鱼藤酮组中脑α-Syn的表达较对照组明显增多(P<0.05)。免疫组化染色显示鱼藤酮组中TH阳性细胞数量较对照组明显减少(P<0.05)。透射电镜显示鱼藤酮组小鼠黑质部可见线粒体、高尔基体不规则肿胀。鱼藤酮组SOD、GSH-PX水平较对照组明显下降(P<0.05),MDA水平较对照组显著增多(P<0.05)。结论:鱼藤酮小剂量持续灌胃可在脑内诱发形成α-Syn寡聚体,α-Syn寡聚体可能经氧化应激途径导致多巴胺神经元损伤。展开更多
文摘Objective To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic （DAergic） neurons for Parkinson＇s disease （PD） research and to determine the effect of differentiation on this cell model. Date sources The data of this review were selected from the original reports and reviews related to SH-SY5Y cells published in Chinese and foreign journals （Pubmed 1973 to 2009）. Study selection After searching the literature, 60 articles were selected to address this review. Results The SH-SY5Y cell line has become a popular cell model for PD research because this cell line posses many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-13-hydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained. However, different differentiating agents induce different neuronal phenotypes and biochemical changes. For example, retinoic acid induces differentiation toward a cholinergic neuronal phenotype and increases the susceptibility of SH-SY5Y cells to neurotoxins and neuroprotective agents, whereas treatment with retinoic acid followed by phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in a DAergic neuronal phenotype and decreases the susceptibility of cells to neurotoxins and neuroprotective agents. Some differentiating agents also alter kinetics of 1-methyl-4-phenyl-pyridinium （MPP~） uptake, making SH-SY5Y cells more similar to primary mesencephalic neurons. Conclusions Differentiated and undifferentiated SH-SY5Y cells have been widely used as a cell model of DAergic neurons for PD research. Some differentiating agents afford SH-SY5Y cells with more potential for studying neurotoxiclty and neuroprotection and are thus more relevant to experimental PD research.
基金supported by the Medical and Health Technology Development Plan of Shandong Province of China,No.2011HD009(to AHW)the Chinese Medicine Science and Technology Development Plan Project of Shandong Province of China,No.2017-163(to AHW)+1 种基金the Natural Science Foundation of Shandong Province of China,No.ZR2016HP23(to AHW)the Science and Technology Development Plan Project of Taian City of China,No.2017NS0151(to XCS)
文摘Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites
文摘目的:通过鱼藤酮持续灌胃构建的帕金森病小鼠模型研究α-突触核蛋白寡聚体(α-Syn)的毒性作用机制。方法:48只老年雄性C57小鼠随机分为鱼藤酮组和对照组,每组24只,鱼藤酮组灌注0.01 mL/g鱼藤酮氯仿溶液,对照组灌注0.01 m L/g氯仿溶液,均连续灌胃12周。于灌胃后取脑,行蛋白质印迹实验检测α-Syn表达水平、透射电镜观察中脑黑质神经元超微结构;于灌胃前、后取脑,免疫组化染色观察黑质部位酪氨酸羟化酶(TH)阳性细胞密度,并检测脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)和丙二醛(MDA)水平。结果:灌胃12周后,Western blot显示鱼藤酮组中脑α-Syn的表达较对照组明显增多(P<0.05)。免疫组化染色显示鱼藤酮组中TH阳性细胞数量较对照组明显减少(P<0.05)。透射电镜显示鱼藤酮组小鼠黑质部可见线粒体、高尔基体不规则肿胀。鱼藤酮组SOD、GSH-PX水平较对照组明显下降(P<0.05),MDA水平较对照组显著增多(P<0.05)。结论:鱼藤酮小剂量持续灌胃可在脑内诱发形成α-Syn寡聚体,α-Syn寡聚体可能经氧化应激途径导致多巴胺神经元损伤。
