This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotroph...This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation.The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially(brain-derived neurotrophic factor to neurotrophin 4/5).This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration.Occlusive and additive effects of both neurotrophins are accompanied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor.The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.展开更多
BACKGROUND： Neurotrophin-4 （NT-4） can promote neuronal growth, development, differentiation, maturation, and survival. NT-4 can also improve recovery and regeneration of injured neurons, but cannot pass through the...BACKGROUND： Neurotrophin-4 （NT-4） can promote neuronal growth, development, differentiation, maturation, and survival. NT-4 can also improve recovery and regeneration of injured neurons, but cannot pass through the blood-brain barrier, which limits its activity in the central nervous system. Delivering NT-4 into the central nervous system v/a cells or vectors may have therapeutic benefit. OBJECTIVE： To construct a recombinant vector with a human embryonic brain-derived NT-4 gene and pEGFP-NI. DESIGN, TIME AND SETTING： Neural genetic engineering experiment. The study was performed at the Neuroscience Institute of Kunming Medical College between October 2007 and March 2008. MATERIALS： The pEGFP-N1 plasmid vector was provided by Kunming Institute of Zoology, Chinese Academy of Sciences; embryonic brain tissues were provided by the First Affiliated Hospital of Kunming Medical College. TRIzol RNA extraction Kit was purchased from Sigma （USA）, One Step RNA PCR Kit （AMV） etc. were from Takara （Dalian, China）. METHODS： Total RNA was extracted from human embryonic brain tissues using Trizol. The agarose gel electrophoresis showed two bands： 18 S and 28 S, which were essential subunits of total RNA. The human NT-4 DNA was obtained via RT-PCR and inserted into the pEGFP-N1 vector using ligation and transformation reaction. MAIN OUTCOME MEASURES： The sequencing results of the DNA in the recombinant of NT-4- pEGFP-NI. RESULTS： The NT-4-pEGFP-N1 vector was sequence-verified and showed the expected molecular weight. CONCLUSION： The recombinant of NT-4-pEGFP-N1 was constructed successfully in vitro.展开更多
基金supported by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica Grants No.216515 and IN 211718。
文摘This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation.The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially(brain-derived neurotrophic factor to neurotrophin 4/5).This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration.Occlusive and additive effects of both neurotrophins are accompanied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor.The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.
基金Supported by:the Scientific Research Foundation of Yunnan Provincial Education Academy,No.07C10388
文摘BACKGROUND： Neurotrophin-4 （NT-4） can promote neuronal growth, development, differentiation, maturation, and survival. NT-4 can also improve recovery and regeneration of injured neurons, but cannot pass through the blood-brain barrier, which limits its activity in the central nervous system. Delivering NT-4 into the central nervous system v/a cells or vectors may have therapeutic benefit. OBJECTIVE： To construct a recombinant vector with a human embryonic brain-derived NT-4 gene and pEGFP-NI. DESIGN, TIME AND SETTING： Neural genetic engineering experiment. The study was performed at the Neuroscience Institute of Kunming Medical College between October 2007 and March 2008. MATERIALS： The pEGFP-N1 plasmid vector was provided by Kunming Institute of Zoology, Chinese Academy of Sciences; embryonic brain tissues were provided by the First Affiliated Hospital of Kunming Medical College. TRIzol RNA extraction Kit was purchased from Sigma （USA）, One Step RNA PCR Kit （AMV） etc. were from Takara （Dalian, China）. METHODS： Total RNA was extracted from human embryonic brain tissues using Trizol. The agarose gel electrophoresis showed two bands： 18 S and 28 S, which were essential subunits of total RNA. The human NT-4 DNA was obtained via RT-PCR and inserted into the pEGFP-N1 vector using ligation and transformation reaction. MAIN OUTCOME MEASURES： The sequencing results of the DNA in the recombinant of NT-4- pEGFP-NI. RESULTS： The NT-4-pEGFP-N1 vector was sequence-verified and showed the expected molecular weight. CONCLUSION： The recombinant of NT-4-pEGFP-N1 was constructed successfully in vitro.
