Background Neuropathologically, Alzheimer disease (AD) is characterized by the presence of extracellular plaques enriched in β-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is un...Background Neuropathologically, Alzheimer disease (AD) is characterized by the presence of extracellular plaques enriched in β-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression. Methods Twenty-four male rats were divided into three groups, and each group had 8 rats: control, sham-operated, and Aβ25-35 injected AD model groups. AD rat models were created by unilateral injections of Aβ25-35 into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 (PHF-1) antibody and paired helical filament-tau (AT8) antibody. The expressions of glycogen synthase kinase-3β (GSK-3β) and p38 mitogen-activated protein kinase (P38MAPK) mRNA were observed by in situ hybridization. Results Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 (PHF-1) in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density (OD) values of the proteins were significantly higher (AT8: in CA2: 0.318±0.037 vs. 0.135±0.028, 0.136±0.031; in frontal cortex: 0.278±0.040 vs. 0.130±0.028, 0.190±0.037. PHF-1 : in CA2: 0.386±0.034 vs. 0.139±0.010, 0.193±0.041; in frontal cortex: 0.395±0.050 vs. 0.159±0.030, 0.190±0.044, respectively, P 〈0.01); the number of GSK-3β mRNA and P38MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus (GSK-3β-mRNA: in CA2:0.384±0.012 vs. 0.190±0.015, 0.258±0.064; in frontal cortex: 0.398±0.018 vs. 0.184±0.031, 0.218±0.049. P38MAPK mRNA: in CA2:0.409±0.038 vs. 0.161±0.041, 0.189±0.035; in frontal cortex: 0.423±0.070 vs. 0.160±0.032, 0.203±0.053, respectively, P 〈0.01). Conclusion Unilateral injection of Aβ25-35 into the rat amygdala increases the generation of aberrant phosphorylated tau by increasing GSK-3β and PasMAPKgene expression, that accelerates the process of Alzhemer's disease.展开更多
Background Aging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular ...Background Aging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells (BMSCs) can improve the cognitive function induced by D-gal injection plus 2VO.Methods Totally 30 male Sprague-Dawley rats were divided into 5 groups equivalently: control group, D-gal group,D-gal+2VO group, D-gal+2VO+saline water group, and D-gal+2VO+BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance (ANOVA) was used for significance analysis of 5 groups at 6 weeks post transplantation;moreover, Tamhane's test (equal variance not assumed) and least significant difference (LSD) test (equal variance assumed) were used for pairwise comparison in Morris water maze (MWM).Results Transplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal+2VO+BMSC group showed significant improvement than the D-gal+2VO group but was still obviously worse than the control group (both P <0.05).There was no significant difference in swimming speed for all 5 groups.Conclusions D-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.展开更多
基金This study was supported by the grants from the National Natural Science Foundation of China (No. 30971029), Fund of Shanghai Science and Technology Committee (No. 08411950900), and Young Excellent Talents Award of Tongji University (No. 2006KJ067).
文摘Background Neuropathologically, Alzheimer disease (AD) is characterized by the presence of extracellular plaques enriched in β-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression. Methods Twenty-four male rats were divided into three groups, and each group had 8 rats: control, sham-operated, and Aβ25-35 injected AD model groups. AD rat models were created by unilateral injections of Aβ25-35 into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 (PHF-1) antibody and paired helical filament-tau (AT8) antibody. The expressions of glycogen synthase kinase-3β (GSK-3β) and p38 mitogen-activated protein kinase (P38MAPK) mRNA were observed by in situ hybridization. Results Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 (PHF-1) in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density (OD) values of the proteins were significantly higher (AT8: in CA2: 0.318±0.037 vs. 0.135±0.028, 0.136±0.031; in frontal cortex: 0.278±0.040 vs. 0.130±0.028, 0.190±0.037. PHF-1 : in CA2: 0.386±0.034 vs. 0.139±0.010, 0.193±0.041; in frontal cortex: 0.395±0.050 vs. 0.159±0.030, 0.190±0.044, respectively, P 〈0.01); the number of GSK-3β mRNA and P38MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus (GSK-3β-mRNA: in CA2:0.384±0.012 vs. 0.190±0.015, 0.258±0.064; in frontal cortex: 0.398±0.018 vs. 0.184±0.031, 0.218±0.049. P38MAPK mRNA: in CA2:0.409±0.038 vs. 0.161±0.041, 0.189±0.035; in frontal cortex: 0.423±0.070 vs. 0.160±0.032, 0.203±0.053, respectively, P 〈0.01). Conclusion Unilateral injection of Aβ25-35 into the rat amygdala increases the generation of aberrant phosphorylated tau by increasing GSK-3β and PasMAPKgene expression, that accelerates the process of Alzhemer's disease.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 81000492), and Young Excellent Talents Award of Shanghai 10th People's Hospital (No.10rq110).
文摘Background Aging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells (BMSCs) can improve the cognitive function induced by D-gal injection plus 2VO.Methods Totally 30 male Sprague-Dawley rats were divided into 5 groups equivalently: control group, D-gal group,D-gal+2VO group, D-gal+2VO+saline water group, and D-gal+2VO+BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance (ANOVA) was used for significance analysis of 5 groups at 6 weeks post transplantation;moreover, Tamhane's test (equal variance not assumed) and least significant difference (LSD) test (equal variance assumed) were used for pairwise comparison in Morris water maze (MWM).Results Transplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal+2VO+BMSC group showed significant improvement than the D-gal+2VO group but was still obviously worse than the control group (both P <0.05).There was no significant difference in swimming speed for all 5 groups.Conclusions D-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.