CAJ | 학술논문

背景:神经生长因子能够促进胆碱能神经元的分化,决定轴突的生长,并可参与损伤神经的再生和功能修复.目的:进一步验证神经生长因子预处理对拟阿尔茨海默病模型大鼠脑内神经原纤维缠结和磷酸化 Tau 蛋白表达的影响.方法:将3-5月龄雄性 Wistar 大鼠随机分为3组:模型组将冈田酸微量注射至拟大鼠海马 CA1区建立拟阿尔茨海默病大鼠模型;预处理组于造模前将神经生长因子注射至侧脑室;对照组用同样方法注入等体积的二甲亚砜作为对照.通过 Morris 水迷宫观察上述大鼠的行为学变化,分别用改进的 Bielschowsky 染色观察海马 CA1区神经原纤维缠结,用免疫组织化学和免疫印迹法观察海马区磷酸化 Tau 蛋白表达的变化.结果与结论:拟阿尔茨海默病模型组大鼠出现认知、学习记忆能力减退;与对照组比较,模型组海马 CA1区出现较多神经原纤维缠结,而且磷酸化的 Tau 蛋白表达增多;神经生长因子预处理组大鼠的上述症状明显改善.提示神经生长因子预处理可以显著改善拟阿尔茨海默病模型大鼠的学习记忆能力,抑制神经原纤维缠结的形成,减少磷酸化Tau 蛋白的表达.
배경:신경생장인자능구촉진담감능신경원적분화,결정축돌적생장,병가삼여손상신경적재생화공능수복.목적:진일보험증신경생장인자예처리대의아이자해묵병모형대서뇌내신경원섬유전결화린산화 Tau 단백표체적영향.방법:장3-5월령웅성 Wistar 대서수궤분위3조:모형조장강전산미량주사지의대서해마 CA1구건립의아이자해묵병대서모형;예처리조우조모전장신경생장인자주사지측뇌실;대조조용동양방법주입등체적적이갑아풍작위대조.통과 Morris 수미궁관찰상술대서적행위학변화,분별용개진적 Bielschowsky 염색관찰해마 CA1구신경원섬유전결,용면역조직화학화면역인적법관찰해마구린산화 Tau 단백표체적변화.결과여결론:의아이자해묵병모형조대서출현인지、학습기억능력감퇴;여대조조비교,모형조해마 CA1구출현교다신경원섬유전결,이차린산화적 Tau 단백표체증다;신경생장인자예처리조대서적상술증상명현개선.제시신경생장인자예처리가이현저개선의아이자해묵병모형대서적학습기억능력,억제신경원섬유전결적형성,감소린산화Tau 단백적표체.
BACKGROUND: Nerve growth factor (NGF) can promote the differentiation of cholinergic neuron, determine the growth of axons and involve in the regeneration and functional recovery of injured nerve. OBJECTIVE: To further validate the effects of NGF pretreatment on neurofibril ary tangles (NFT) and phosphorylated Tau protein expression in the hippocampal CA1 region of Alzheimer’s disease (AD)-like model rats. METHODS: Male Wistar rats (3-5 months old) were randomly divided into control group, AD-like model group and NGF pretreatment group. In the AD-like model group, AD-like rat model was established by injecting okadaic acid into the hippocampal CA1 region. In the NGF pretreatment group, NGF was injected into the lateral ventricle of the brain in rats before okadaic acid was injected for establishing the AD-like animal model. The rats of the control group were injected an equal volume of dimethyl sulfoxide using the same method. The behavior changes of rats were observed by Morris water maze. Then, the NFT in hippocampal CA1 region was detected by improved Bielschowsky staining. Besides, the changes of phosphorylated Tau protein expression in the hippocampal CA1 region were observed by immunohistochemical and western blot methods. RESULTS AND CONCLUSION: Learning disabilities and memory deficits in the AD-like model rats were found. Compared with the control group, in the model group, there were more NFTs; in addition, the phosphorylated Tau protein expression was increased in the hippocampus. However, the above symptoms in the rats of the NGF pretreated group were improved obviously. These results suggest that NGF pretreatment can significantly improve learning and memory capabilities of the AD-like model rats, inhibit NFT formation and decrease the expression of phosphorylated Tau protein.