基于 Wnt/-连环蛋白通路，番茄红素负载型微乳调控 A 诱导 AD 大鼠的神经发生。
Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with A-Induced Alzheimer's Disease Rats Based on the Wnt/-catenin Pathway.
机构信息
Department of Geriatric Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
First People's Hospital of Jinan, Jinan, Shandong 250000, China.
出版信息
Neural Plast. 2021 Sep 6;2021:5519330. doi: 10.1155/2021/5519330. eCollection 2021.
OBJECTIVE
To investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid - (A-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/-catenin pathway.
METHODS
Healthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/-catenin pathway-related proteins, respectively.
RESULTS
On the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of A-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU, Dcx, BrdU/Neun, BrdU/Dcx cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1 and Iba1/BrdU cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/-catenin pathway by upregulating Wnt3a, -catenin, Disheveled (Dvl), and p-GSK3 and downregulating p--catenin and GSK3.
CONCLUSION
LME attenuates cognitive impairment in A-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/-catenin pathway.
目的
基于 Wnt/-连环蛋白通路，研究番茄红素载微乳（LME）对淀粉样蛋白-β（A-β）诱导的阿尔茨海默病（AD）大鼠海马齿状回（DG）和侧脑室下区（SVZ）认知功能和神经发生的影响。
方法
将健康 Wistar 大鼠分为 4 组：空白对照组（CON）、AD 对照组、传统番茄红素组（LOO）和 LME 组。CON 和 AD 组给予生理盐水灌胃，LOO 组给予传统番茄红素灌胃，LME 组给予番茄红素载微乳灌胃。灌胃 3 周后进行行为学测试。免疫荧光标记细胞观察海马 DG 和 SVZ 区新生神经细胞的分化和成熟。qRT-PCR 和 Western blot 分别检测神经发生基因和 Wnt/-连环蛋白通路相关蛋白的表达。
结果
在 Morris 水迷宫测试中，LME 大鼠在搜索平台上的运动轨迹明显缩短，逃避潜伏期时间减少，原平台象限停留时间增加。此外，当平台被移除时，更多的 LME 大鼠穿过平台。因此，LME 可以改善 A 诱导的 AD 大鼠的空间学习和记忆。qRT-PCR 结果显示，LME 显著增加了调节神经发生的 Reelin、Nestin 和 Pax6 基因的表达。免疫荧光显示，LME 可显著增加 DG 和 SVZ 区的 BrdU、Dcx、BrdU/Neun、BrdU/Dcx 细胞，从而促进神经发生。LME 还减少了 Iba1 和 Iba1/BrdU 细胞的数量，从而减轻神经炎症反应。Western blot 结果显示，LME 通过上调 Wnt3a、-catenin、Disheveled（Dvl）和 p-GSK3，下调 p--catenin 和 GSK3，上调 Wnt/-连环蛋白通路。
结论
LME 通过上调 Wnt/-连环蛋白通路促进海马和 SVZ 区神经发生，减轻 A 诱导的 AD 大鼠认知障碍。
Zotero 插件