Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
The present study established rat models of middle cerebral artery ischemia/reperfusion using the thread method. Rats performed willed-movement （climbing a ladder or wall in a box） when induced by food and water. Re...The present study established rat models of middle cerebral artery ischemia/reperfusion using the thread method. Rats performed willed-movement （climbing a ladder or wall in a box） when induced by food and water. Results revealed that Longa scores of neurological deficits significantly decreased in the willed-movement group at 15 days after reperfusion, while expression of glial fibrillary acidic protein, neurotrophic factor-3, and growth-associated protein-43 significantly increased at 7 and 15 days after reperfusion. Results suggested that willed-movement ameliorated neurological deficits by increasing expression of glial fibriliary acidic protein, neurotrophic factor-3, and growth-associated protein-43.展开更多
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
基金the Science and Technology Projects from Science and Technology Agency,Hunan Province,China,No. 2011FJ3206
文摘The present study established rat models of middle cerebral artery ischemia/reperfusion using the thread method. Rats performed willed-movement （climbing a ladder or wall in a box） when induced by food and water. Results revealed that Longa scores of neurological deficits significantly decreased in the willed-movement group at 15 days after reperfusion, while expression of glial fibrillary acidic protein, neurotrophic factor-3, and growth-associated protein-43 significantly increased at 7 and 15 days after reperfusion. Results suggested that willed-movement ameliorated neurological deficits by increasing expression of glial fibriliary acidic protein, neurotrophic factor-3, and growth-associated protein-43.
