Cajal-Retzius cells are reelin-secreting neurons in the marginal zone of the neocortex and hippocampus. The aim of this study was to investigate Cajal-Retzius cells in Alzheimer's disease pathology. Results revealed ...Cajal-Retzius cells are reelin-secreting neurons in the marginal zone of the neocortex and hippocampus. The aim of this study was to investigate Cajal-Retzius cells in Alzheimer's disease pathology. Results revealed that the number of Cajal-Retzius cells markedly reduced with age in both wild type and in mice over-expressing the Swedish double mutant form of amyloid precursor protein 695 (transgenic (Tg) 2576 mice). Numerous reelin-positive neurons were positive for activated caspase 3 in Tg2576 mice, suggesting that Cajal-Retzius neuronal loss occurred via apoptosis in this Alzheimer's disease model. Compared with wild type, the number of Cajal-Retzius cells was significantly lower in Tg2576 mice. Western blot analysis confirmed that reelin levels were markedly lower in Tg2576 mice than in wild-type mice. The decline in Cajal-Retzius cells in Tg2576 mice was found to occur concomitantly with the onset of Alzheimer's disease amyloid pathology and related behavioral deficits. Overall, these data indicated that Cajal-Retzius cell loss occurred with the onset and development of Alzheimer's disease.展开更多
Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease (AD), especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-...Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease (AD), especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-κB (p50) expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. Results Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF- κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 (P 0.01 or P 0.05). Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB. Conclusion The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.展开更多
This study aims to discuss the effect of preventing pathological changes and cognitive degeneration of Tg2576 mice by inoculating the subunit fragment of Aβ vaccine.Thirty-two Tg2576 mice were randomly divided into f...This study aims to discuss the effect of preventing pathological changes and cognitive degeneration of Tg2576 mice by inoculating the subunit fragment of Aβ vaccine.Thirty-two Tg2576 mice were randomly divided into four groups, each having eight mice:Group I, the control group, inoculated with adjuvants;Group II, the Aβ42 group, inoculated with Aβ42 vaccine;Group Ⅲ, the Aβ1―15 group, inoculated with Aβ1―15 vaccine;and Group IV, the Aβ36―42 group, inoculated with Aβ36―42 vaccine.The titer of the serum anti-body against Aβ42(Group II) was significantly higher than that of the control group(Group I), and a low level of antibodies could be detected in the brain homogenate in the three vaccine-inoculated groups.Morris water maze test showed that the Aβ42 group, Aβ1―15 group and Aβ36―42 group were obviously im-proved compared with the control group.The cultured splenocytes sampled from each group were induced by Con A or their respective antigens, and the cell proliferation of the three vaccine-inoculated groups was significantly higher than that of the control group.In the Aβ42 group, IL2 and IFN-γ were relatively low and IL4 and IL10 were relatively high.By contrast, IL4 and IL10 were much higher in the Aβ1―15 group and IL2 and IFN-γ were much higher in the Aβ36―42 group.The immunohistochemical test showed a large number of senile plaques in the brain cortex and hippocampus of the mice in the con-trol group, no senile plaque in the brain of the Aβ1―15 group and Aβ42 group mice, and a small number of senile plaques in the brain of the Aβ36―42 group mice.The results suggest that the subunit fragment of Aβ1―15 vaccine could prevent not only cognitive and behavioral degeneration but also Aβ deposition and formation of senile plaques in Tg2576 mice.展开更多
基金supported by the National Natural Science Foundation of China,No.31070952,81071029the Joint Funds of the NSFC with Henan Provence Government for Fostering Talents,No.U1204809the Henan Province Science Research Project,No.132102310111
文摘Cajal-Retzius cells are reelin-secreting neurons in the marginal zone of the neocortex and hippocampus. The aim of this study was to investigate Cajal-Retzius cells in Alzheimer's disease pathology. Results revealed that the number of Cajal-Retzius cells markedly reduced with age in both wild type and in mice over-expressing the Swedish double mutant form of amyloid precursor protein 695 (transgenic (Tg) 2576 mice). Numerous reelin-positive neurons were positive for activated caspase 3 in Tg2576 mice, suggesting that Cajal-Retzius neuronal loss occurred via apoptosis in this Alzheimer's disease model. Compared with wild type, the number of Cajal-Retzius cells was significantly lower in Tg2576 mice. Western blot analysis confirmed that reelin levels were markedly lower in Tg2576 mice than in wild-type mice. The decline in Cajal-Retzius cells in Tg2576 mice was found to occur concomitantly with the onset of Alzheimer's disease amyloid pathology and related behavioral deficits. Overall, these data indicated that Cajal-Retzius cell loss occurred with the onset and development of Alzheimer's disease.
基金supported by theNational Natural Science Foundation of China (No. 30670688,30771140)the Natural Science Foundation of Education De-partment of Henan Province (No. 2007180008)+1 种基金the Natural Science Key Program of Henan University (No. 2008YBGG048)the International Cooperation Program of Science andTechnique Department of Henan Province, China (No.094300510044)
文摘Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease (AD), especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-κB (p50) expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. Results Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF- κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 (P 0.01 or P 0.05). Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB. Conclusion The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.
基金Supported by the National Natural Science Foundation of China (Grant No. 30400512)Natural Science Foundation of Guangdong Province (Grant No. 20013137)+1 种基金Science and Technology Project of Guangzhou City (Grant No. 2004Z3-E0151)Social Development Project of Guangdong Province (Grant No. 2005B10401047)
文摘This study aims to discuss the effect of preventing pathological changes and cognitive degeneration of Tg2576 mice by inoculating the subunit fragment of Aβ vaccine.Thirty-two Tg2576 mice were randomly divided into four groups, each having eight mice:Group I, the control group, inoculated with adjuvants;Group II, the Aβ42 group, inoculated with Aβ42 vaccine;Group Ⅲ, the Aβ1―15 group, inoculated with Aβ1―15 vaccine;and Group IV, the Aβ36―42 group, inoculated with Aβ36―42 vaccine.The titer of the serum anti-body against Aβ42(Group II) was significantly higher than that of the control group(Group I), and a low level of antibodies could be detected in the brain homogenate in the three vaccine-inoculated groups.Morris water maze test showed that the Aβ42 group, Aβ1―15 group and Aβ36―42 group were obviously im-proved compared with the control group.The cultured splenocytes sampled from each group were induced by Con A or their respective antigens, and the cell proliferation of the three vaccine-inoculated groups was significantly higher than that of the control group.In the Aβ42 group, IL2 and IFN-γ were relatively low and IL4 and IL10 were relatively high.By contrast, IL4 and IL10 were much higher in the Aβ1―15 group and IL2 and IFN-γ were much higher in the Aβ36―42 group.The immunohistochemical test showed a large number of senile plaques in the brain cortex and hippocampus of the mice in the con-trol group, no senile plaque in the brain of the Aβ1―15 group and Aβ42 group mice, and a small number of senile plaques in the brain of the Aβ36―42 group mice.The results suggest that the subunit fragment of Aβ1―15 vaccine could prevent not only cognitive and behavioral degeneration but also Aβ deposition and formation of senile plaques in Tg2576 mice.