Résumé
Objective To investigate the effects of CTNND2 knockout on cerebellar neuronal development and motor function in mice, as well as its possible mechanisms. Methods The mice were divided into two groups (n = 10 in each group), all of them were 7 weeks old : wild-type (WT) C57BL/6J mice were treated as control group, and homozygous of CTNND2 knockout (CTNND2 7) mice were treated as experimental group, the genotype of CTNND2 7 mice were detected with PCR. The motor function of two groups were detected by beam walking test, hanging wire test and gait analysis test. The changes of cerebellar Purkinje cells were detected by immunofluorescence staining and Golgi staining. Western blotting was performed to detect the expression levels of synapse-associated proteins phosphorylated synapsin 1 (p-Synl), synapsin 1 (Synl), ELKS and postsynaptic density protein 95(PSD95), as well as phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and mammalian target of rapamycin (mTOR). Results Compared with the WT mice, except the increase in time to traverse the beam, there was a decrease in the proportion of pass on the beam, or latency to fall from the hanging wire, or score of hanging wire, or fore-stride length and hind-stride length of CTNND2 7 mice. There was also a decrease in numbers of Purkinje cells and its dendritic arborization in cerebellum of CTNND2 7 mice. The ratio of p-Synl/ Synl, p-Akt/Akt and p-mTOR/mTOR, as well as the expression levels of ELKS, PSD95 and PI3K were lower than those of WT mice. Conclusion CTNND2 knockout can affect the number and dendritic architecture of Purkinje cells, as well as synthesis of synapse-associated proteins in cerebellum by down-regulating PI3K/Akt/mT0R signaling pathway, resulting in cerebellar developmental disorder, thereby affecting motor function of mice.
Résumé
Objective To establish an animal model of aging,to observe changes related to cognitive impairment and depression-like behavior,and to explore the mechanisms of the two diseases caused by the model.Methods Male Sprague-Dawley (SD) rats were treated with D-galactose and alchlor;after simultaneous administration of both drugs,their learning and memory abilities were assessed using the Morris water maze test.The depression-like behavioral changes were observed in the forced swimming test.Golgi staining was performed to observe the development of hippocampal neurons;oxidative stress index changes in superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were analyzed in the hippocampus.Results Compared with a control group,rats in the model group showed reduced escape latency (P ＜ 0.05) from the platform in the water maze,reduced residence time on and a reduced number of times passing through the platform (P ＜ 0.05);the real time in the water during the forced swimming test was significantly prolonged (P ＜ 0.01).Golgi staining indicated that dendritic spine density in the hippocampus in model rats was decreased (P ＜ 0.01),as was hippocampus SOD activity (P ＜ 0.05),while MDA levels were increased (P ＜ 0.05).Conclusion We established a new animal model of aging with cognitive impairment and depression.The common disease mechanisms of these two diseases might be related to the destruction of the nervous system during the process of overload caused by free radicals and the resulting metabolic imbalance.
Résumé
This study was aimed to observe the changes of dendritic spine density in different regions of brain among spleen-yindeficiency dementia (SYDD) model rats, in order to investigate the effects ofZi-Bu Pi-Yin Recipe (ZBPYR) on dendritic spines. Spleen-yindeficiency (SYD) rats were modeled by classical method. And incubatedβ-Amyloid 1-40 (Aβ1-40) was injected into the hippocampus of each rat to make SYDD model, which received the administration of ZBPYR. Golgi staining was used to stain dendritic spine in different regions of brain in rat model for the observation of the amount and shape. The results showed that dendritic spine density in different regions of hippocampus and cortex in SYDD group was reduced than that of the SYD group. Compared with the dementia group and the SYDD group, the dendritic spine density in different regions of hippocampus and cortex of the SYDD + ZBPYR group was increased. Compared with the blank control group, the dendritic spine density in different regions of hippocampus and cortex in rats from the dementia group was reduced. It was concluded that there were different degrees of reducing in the dendritic spine density of different brain regions in SYDD group. ZBPYR improved the learning and memory impairment, which might be related to the maintenance of dendritic spine density in different brain regions.