OBJECTIVE To explore the changes of calretinin interneurons in APP/PS1 mouse model and their correlation with the pathological features of Alzheimer disease.METHODS The morphological differences between the brain regi...OBJECTIVE To explore the changes of calretinin interneurons in APP/PS1 mouse model and their correlation with the pathological features of Alzheimer disease.METHODS The morphological differences between the brain regions of control and transgenic(TG) mice were detected by Nissl staining.By immunofluorescence histochemistry and western blotting,the expression of related proteins was detected,including GAD65/67,calretinin and Aβ1-42.At the same time,in terms of behavioral experiments,the motor ability,the level of fear and cognitive level of control and transgenic mice were tested through open-field test,elevated plus maze and novel object recognition(NOR) experiment.RESULTS According to Nissl staining results,compared with the control group,the number of cells in glomerular layer(GL) and granule cell layer(GCL) of olfactory bulb in the TG group was significantly reduced.Meanwhile,in the hippocampus,compared with the control group,the ventral CA1 and CA3 is dysplastic in APP/PS1 group.Moreover,the morphology of subgranular zone(SGZ) layer cells in the dorsal DG significantly changed and the number of cells in hilar regions significantly decreased in the TG group.Other brain regions associated with cognition,including the piriform cortex,entorhinal cortex and the prefrontal cortex,showed no significant changes between the control and TG group.By Western blotting experiment,compared with the control mice,it was found that the expression of GAD65/67 and calretinin in the olfactory bulb and hippocampus was significantly decreased in the TG group.In detail,the level of the protein in the relevant brain regions was detected by immunofluorescence histochemistry(IHC).The expression of calretinin in GL of the olfactory bulb and the hippocampal DG region was significantly decreased,which was correlated with the distribution of Aβ1-42 by IHC.In the part of functional behavioral experiment,compared with the control mice,the total distance of movement in 6 M TG group mice was significantly increased in the open field test.In the elevated plus maze test,there were no significant differences between control and TG group.In addition,the mice of TG group lacked the ability to distinguish between old and new objects in the NOR experiment.CONCLUSION The number of calretinin interneurons in olfactory bulb and hippocampus decreased significantly in APP/PS1 mouse model,which is more correlated with the distribution of Aβ1-42 and functional disorders,including the enhancement of spontaneous locomotor activity and cognitive impairment.展开更多
基金CAMS Innovation Fund for Medical Sciences(CIFMS) (2016-I2M-1-004).
文摘OBJECTIVE To explore the changes of calretinin interneurons in APP/PS1 mouse model and their correlation with the pathological features of Alzheimer disease.METHODS The morphological differences between the brain regions of control and transgenic(TG) mice were detected by Nissl staining.By immunofluorescence histochemistry and western blotting,the expression of related proteins was detected,including GAD65/67,calretinin and Aβ1-42.At the same time,in terms of behavioral experiments,the motor ability,the level of fear and cognitive level of control and transgenic mice were tested through open-field test,elevated plus maze and novel object recognition(NOR) experiment.RESULTS According to Nissl staining results,compared with the control group,the number of cells in glomerular layer(GL) and granule cell layer(GCL) of olfactory bulb in the TG group was significantly reduced.Meanwhile,in the hippocampus,compared with the control group,the ventral CA1 and CA3 is dysplastic in APP/PS1 group.Moreover,the morphology of subgranular zone(SGZ) layer cells in the dorsal DG significantly changed and the number of cells in hilar regions significantly decreased in the TG group.Other brain regions associated with cognition,including the piriform cortex,entorhinal cortex and the prefrontal cortex,showed no significant changes between the control and TG group.By Western blotting experiment,compared with the control mice,it was found that the expression of GAD65/67 and calretinin in the olfactory bulb and hippocampus was significantly decreased in the TG group.In detail,the level of the protein in the relevant brain regions was detected by immunofluorescence histochemistry(IHC).The expression of calretinin in GL of the olfactory bulb and the hippocampal DG region was significantly decreased,which was correlated with the distribution of Aβ1-42 by IHC.In the part of functional behavioral experiment,compared with the control mice,the total distance of movement in 6 M TG group mice was significantly increased in the open field test.In the elevated plus maze test,there were no significant differences between control and TG group.In addition,the mice of TG group lacked the ability to distinguish between old and new objects in the NOR experiment.CONCLUSION The number of calretinin interneurons in olfactory bulb and hippocampus decreased significantly in APP/PS1 mouse model,which is more correlated with the distribution of Aβ1-42 and functional disorders,including the enhancement of spontaneous locomotor activity and cognitive impairment.
