在早期阿尔茨海默病小鼠模型中,电针促进齿状回神经发生并改善模式分离。

IF 4.3 2区 生物学 Q1 BIOLOGY
Yanyi Ding, Long Li, Sinuo Wang, Yajun Cao, Minguang Yang, Yaling Dai, Huawei Lin, Jianhong Li, Yulu Liu, Zhifu Wang, Weilin Liu, Jing Tao
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引用次数: 0

摘要

背景:模式分离受损发生在阿尔茨海默病(AD)早期,海马齿状回(DG)神经发生参与模式分离。在这里,我们研究了电针(EA)是否可以通过促进AD早期海马DG颗粒细胞新生介导的模式分离来改善空间记忆辨别障碍。方法:对5只家族性AD突变(5 × FAD)小鼠进行百会穴、神汀穴EA治疗4周。在EA期间,小鼠每天2次腹腔注射BrdU (50 mg/kg)。将含有Wnt5a shRNA的rAAV注射到双侧DG区,通过检测Wnt5a mRNA水平来评估病毒效率。进行认知行为测试以评估EA治疗对认知功能的影响。干预后免疫组化检测海马DG区Aβ沉积水平;采用免疫荧光和western blotting检测干预后海马DG区BrdU+/CaR+细胞数量、calretinin (CaR)和prospero homobox 1(Prox1)基因表达水平,评估神经发生;干预后采用Western blotting检测Wnt信号通路中FZD2、Wnt5a、DVL2、p-DVL2、CaMKII、p-CaMKII的基因表达水平。结果:认知行为测试显示5 × FAD小鼠模式分离受损(P)。结论:EA可通过调节Wnt5a,促进海马DG未成熟颗粒细胞新生介导的模式分离,改善5 × FAD小鼠空间记忆辨别障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Electroacupuncture promotes neurogenesis in the dentate gyrus and improves pattern separation in an early Alzheimer's disease mouse model.

Background: Impaired pattern separation occurs in the early stage of Alzheimer's disease (AD), and hippocampal dentate gyrus (DG) neurogenesis participates in pattern separation. Here, we investigated whether spatial memory discrimination impairment can be improved by promoting the hippocampal DG granule cell neogenesis-mediated pattern separation in the early stage of AD by electroacupuncture (EA).

Methods: Five familial AD mutations (5 × FAD) mice received EA treatment at Baihui and Shenting points for 4 weeks. During EA, mice were intraperitoneally injected with BrdU (50 mg/kg) twice a day. rAAV containing Wnt5a shRNA was injected into the bilateral DG region, and the viral efficiency was evaluated by detecting Wnt5a mRNA levels. Cognitive behavior tests were conducted to assess the impact of EA treatment on cognitive function. The hippocampal DG area Aβ deposition level was detected by immunohistochemistry after the intervention; The number of BrdU+/CaR+ cells and the gene expression level of calretinin (CaR) and prospero homeobox 1(Prox1) in the DG area of the hippocampus was detected to assess neurogenesis by immunofluorescence and western blotting after the intervention; The gene expression levels of FZD2, Wnt5a, DVL2, p-DVL2, CaMKII, and p-CaMKII in the Wnt signaling pathway were detected by Western blotting after the intervention.

Results: Cognitive behavioral tests showed that 5 × FAD mice had impaired pattern separation (P < 0.001), which could be improved by EA (P < 0.01). Immunofluorescence and Western blot showed that the expression of Wnt5a in the hippocampus was decreased (P < 0.001), and the neurogenesis in the DG was impaired (P < 0.001) in 5 × FAD mice. EA could increase the expression level of Wnt5a (P < 0.05) and promote the neurogenesis of immature granule cells (P < 0.05) and the development of neuronal dendritic spines (P < 0.05). Interference of Wnt5a expression aggravated the damage of neurogenesis (P < 0.05), weakened the memory discrimination ability (P < 0.05), and inhibited the beneficial effect of EA (P < 0.05) in AD mice. The expression level of Wnt pathway related proteins such as FZD2, DVL2, p-DVL2, CAMKII, p-CAMKII increased after EA, but the effect of EA was inhibited after Wnt5a was knocked down. In addition, EA could reduce the deposition of Aβ plaques in the DG without any impact on Wnt5a.

Conclusion: EA can promote hippocampal DG immature granule cell neogenesis-mediated pattern separation to improve spatial memory discrimination impairment by regulating Wnt5a in 5 × FAD mice.

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来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
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