Wen-Jing Ning, Ren-Jun Lv, Ning Xu, Xun-Yao Hou, Chao Shen, Yun-Liang Guo, Zhong-Yu Fan, Na Cao, Xue-Ping Liu
{"title":"番茄红素微乳基于Wnt/β-catenin通路调控a β诱导的阿尔茨海默病大鼠神经发生。","authors":"Wen-Jing Ning, Ren-Jun Lv, Ning Xu, Xun-Yao Hou, Chao Shen, Yun-Liang Guo, Zhong-Yu Fan, Na Cao, Xue-Ping Liu","doi":"10.1155/2021/5519330","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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 <i>β</i>- (A<i>β</i>-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/<i>β</i>-catenin pathway.</p><p><strong>Methods: </strong>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/<i>β</i>-catenin pathway-related proteins, respectively.</p><p><strong>Results: </strong>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<i>β</i>-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<sup>+</sup>, Dcx<sup>+</sup>, BrdU<sup>+</sup>/Neun<sup>+</sup>, BrdU<sup>+</sup>/Dcx<sup>+</sup> cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1<sup>+</sup> and Iba1<sup>+</sup>/BrdU<sup>+</sup> cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/<i>β</i>-catenin pathway by upregulating Wnt3a, <i>β</i>-catenin, Disheveled (Dvl), and p-GSK3<i>β</i> and downregulating p-<i>β</i>-catenin and GSK3<i>β</i>.</p><p><strong>Conclusion: </strong>LME attenuates cognitive impairment in A<i>β</i>-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/<i>β</i>-catenin pathway.</p>","PeriodicalId":51299,"journal":{"name":"Neural Plasticity","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2021-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448994/pdf/","citationCount":"10","resultStr":"{\"title\":\"Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with A<i>β</i>-Induced Alzheimer's Disease Rats Based on the Wnt/<i>β</i>-catenin Pathway.\",\"authors\":\"Wen-Jing Ning, Ren-Jun Lv, Ning Xu, Xun-Yao Hou, Chao Shen, Yun-Liang Guo, Zhong-Yu Fan, Na Cao, Xue-Ping Liu\",\"doi\":\"10.1155/2021/5519330\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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 <i>β</i>- (A<i>β</i>-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/<i>β</i>-catenin pathway.</p><p><strong>Methods: </strong>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/<i>β</i>-catenin pathway-related proteins, respectively.</p><p><strong>Results: </strong>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<i>β</i>-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<sup>+</sup>, Dcx<sup>+</sup>, BrdU<sup>+</sup>/Neun<sup>+</sup>, BrdU<sup>+</sup>/Dcx<sup>+</sup> cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1<sup>+</sup> and Iba1<sup>+</sup>/BrdU<sup>+</sup> cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/<i>β</i>-catenin pathway by upregulating Wnt3a, <i>β</i>-catenin, Disheveled (Dvl), and p-GSK3<i>β</i> and downregulating p-<i>β</i>-catenin and GSK3<i>β</i>.</p><p><strong>Conclusion: </strong>LME attenuates cognitive impairment in A<i>β</i>-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/<i>β</i>-catenin pathway.</p>\",\"PeriodicalId\":51299,\"journal\":{\"name\":\"Neural Plasticity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2021-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448994/pdf/\",\"citationCount\":\"10\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neural Plasticity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/2021/5519330\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neural Plasticity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2021/5519330","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with Aβ-Induced Alzheimer's Disease Rats Based on the Wnt/β-catenin Pathway.
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 β- (Aβ-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/β-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/β-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 Aβ-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/β-catenin pathway by upregulating Wnt3a, β-catenin, Disheveled (Dvl), and p-GSK3β and downregulating p-β-catenin and GSK3β.
Conclusion: LME attenuates cognitive impairment in Aβ-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/β-catenin pathway.
期刊介绍:
Neural Plasticity is an international, interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology. Neural Plasticity publishes research and review articles from the entire range of relevant disciplines, including basic neuroscience, behavioral neuroscience, cognitive neuroscience, biological psychology, and biological psychiatry.