Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers p...Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.展开更多
目的:研究慢性帕金森病模型小鼠行为学、黑质致密部多巴胺神经细胞和纹状体多巴胺转运体(DAT)的变化。方法:利用MPTP和二丙苯磺胺联合注射小鼠5周(每周2次,共10次)制作帕金森病小鼠慢性模型,通过转棒法检测小鼠行为学表现,免疫组织化学...目的:研究慢性帕金森病模型小鼠行为学、黑质致密部多巴胺神经细胞和纹状体多巴胺转运体(DAT)的变化。方法:利用MPTP和二丙苯磺胺联合注射小鼠5周(每周2次,共10次)制作帕金森病小鼠慢性模型,通过转棒法检测小鼠行为学表现,免疫组织化学方法测定黑质内多巴胺能神经细胞的变化,放射自显影技术测定纹状体内DAT的密度。结果:帕金森病小鼠在转棒试验中行为发生明显改变,模型组行为学得分明显低于对照组(895±238 vs 1202±252,P<0.001),酪氨酸羟化酶(TH)阳性细胞数也明显低于对照组(10.4±6.5 vs22.4±8.0,P<0.001)。模型组动物纹状体DAT放射自显影灰度值明显低于对照组(0.2123±0.0316 vs 0.3034±0.0588,P<0.001)。线性回归表明,模型组小鼠黑质致密部TH阳性细胞数及纹状体内DAT密度与对应行为学得分呈明显正相关(r=0.6354,P<0.01)。结论:MPTP和二丙苯磺胺所致的帕金森病小鼠,在行为学、纹状体DAT密度和黑质致密部多巴胺神经细胞量上均有明显改变,提示这种小鼠模型可用于研究帕金森病的发病过程和药物治疗。展开更多
During the long period of time when people have been seeking for an effective therapeutic method for PD, the gene therapy has shown greater and greater advantages over other methods. It can be performed mainly in two ...During the long period of time when people have been seeking for an effective therapeutic method for PD, the gene therapy has shown greater and greater advantages over other methods. It can be performed mainly in two ways: ex vivo and in vivo. With the former, TH gene as well as some neurotrophic factor genes (such as GDNF, BNDF genes) can be invited to some cell lines or primary cells thus forming engineered cells and then implanting them into brain. While with the latter, viral vectors including HSV-1, Ad, AAV that can be utilized to construct recombinant viruses, or non-virus vectors can be used to delived DNA into brain directly. The present review summarizes the recent research advances in the gene therapy for PD, and it is reasonable for us to predict a notable progress in prevention and treatment for PD in the next decade.展开更多
基金supported by grants from National Natural Science Foundation of China(No.81071307,No.30872440,No.81171259)
文摘Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.
文摘目的:研究慢性帕金森病模型小鼠行为学、黑质致密部多巴胺神经细胞和纹状体多巴胺转运体(DAT)的变化。方法:利用MPTP和二丙苯磺胺联合注射小鼠5周(每周2次,共10次)制作帕金森病小鼠慢性模型,通过转棒法检测小鼠行为学表现,免疫组织化学方法测定黑质内多巴胺能神经细胞的变化,放射自显影技术测定纹状体内DAT的密度。结果:帕金森病小鼠在转棒试验中行为发生明显改变,模型组行为学得分明显低于对照组(895±238 vs 1202±252,P<0.001),酪氨酸羟化酶(TH)阳性细胞数也明显低于对照组(10.4±6.5 vs22.4±8.0,P<0.001)。模型组动物纹状体DAT放射自显影灰度值明显低于对照组(0.2123±0.0316 vs 0.3034±0.0588,P<0.001)。线性回归表明,模型组小鼠黑质致密部TH阳性细胞数及纹状体内DAT密度与对应行为学得分呈明显正相关(r=0.6354,P<0.01)。结论:MPTP和二丙苯磺胺所致的帕金森病小鼠,在行为学、纹状体DAT密度和黑质致密部多巴胺神经细胞量上均有明显改变,提示这种小鼠模型可用于研究帕金森病的发病过程和药物治疗。
文摘During the long period of time when people have been seeking for an effective therapeutic method for PD, the gene therapy has shown greater and greater advantages over other methods. It can be performed mainly in two ways: ex vivo and in vivo. With the former, TH gene as well as some neurotrophic factor genes (such as GDNF, BNDF genes) can be invited to some cell lines or primary cells thus forming engineered cells and then implanting them into brain. While with the latter, viral vectors including HSV-1, Ad, AAV that can be utilized to construct recombinant viruses, or non-virus vectors can be used to delived DNA into brain directly. The present review summarizes the recent research advances in the gene therapy for PD, and it is reasonable for us to predict a notable progress in prevention and treatment for PD in the next decade.