藏红花素通过降低DKK3表达来驱动阿尔茨海默病大鼠模型中的肠道微生物群变异。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-05-24 DOI:10.1016/j.brainres.2025.149734

Xiaojia Yang , Meng Jiang , Min Wu , Xin Jin , Xinyu Wang , Lan Lv , Liquan Liu

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引用次数: 0

摘要

背景：阿尔茨海默病（AD）是一种常见的神经退行性疾病。靶向dkk3介导的肠道微生物群（IM）变异是治疗AD的一种有希望的策略。藏红花素可以改变IM分布，抑制DKK3的表达。我们的目的是探讨藏红花素是否通过调节dkk3介导的IM变异来缓解AD。方法：采用大鼠脑内注射Aβ1-42建立AD动物模型。随后，AD大鼠DKK3过表达并给予藏红花素处理。采用Morris水迷宫和被动回避实验评估大鼠的学习记忆能力。分析藏红花素对大鼠脑组织a - β1-42、p-tau水平及血清促炎细胞因子（TNF-α、IL-1β、IL-6）水平的影响。然后观察大鼠海马病理损伤情况。免疫组织化学和Western blot检测DKK3、NeuN、Bax、BCL-2的表达和GSK-3β磷酸化水平。收集大鼠粪便进行16S rRNA测序。结果：藏红花素能提高AD大鼠的学习记忆能力。此外，藏红花素抑制AD大鼠脑a - β1-42和p-tau水平以及血清促炎细胞因子水平。藏花素可减轻AD大鼠海马病理损伤，抑制DKK3、Bax表达和GSK-3β磷酸化，增加NeuN、BCL-2表达。值得注意的是，藏红花素增加了AD大鼠IM的α和β多样性。然而，DKK3过表达逆转了这些情况。此外，藏红花素处理导致Prevotellaceae_NK3B31_group增加，同时减少了Lachnospiraceae UCG-001和Family_XIII_AD3011_group。结论：藏红花素通过调节dkk3介导的IM变异减轻AD，提示dkk3介导的IM变异是AD的潜在治疗靶点。

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Crocin drives intestinal microbiota variation in a rat model of Alzheimer’s disease by reducing DKK3 expression

Background

Alzheimer’s disease (AD) is a common neurodegenerative disease. Targeting DKK3-mediated intestinal microbiota (IM) variation is a promising strategy to treat AD. Crocin can alter IM distribution and inhibit DKK3 expression. We aimed to explore whether Crocin alleviates AD by regulating DKK3-mediated IM variation.

Methods

AD animal models were established by injecting Aβ_1-42 into the brains of rats. Subsequently, AD rats were overexpressed with DKK3 and treated with Crocin. Morris water maze and passive avoidance tests were performed to assess the learning and memory abilities of the rats. The effect of Crocin on brain Aβ_1-42 and p-tau levels, serum proinflammatory cytokine (TNF-α, IL-1β and IL-6) levels were analyzed. Then, hippocampal pathological damage of the rats was evaluated. Furthermore, DKK3, NeuN, Bax, BCL-2 expressions and GSK-3β phosphorylation were measured by immunohistochemistry and Western blot. Moreover, rat feces were collected for 16S rRNA sequencing.

Results

Crocin improved learning and memory abilities of AD rats. Additionally, Crocin inhibited brain Aβ_1-42 and p-tau levels, and serum proinflammatory cytokine levels for AD rats. It was also observed that Crocin attenuated hippocampal pathological damage, inhibited DKK3, Bax expressions and GSK-3β phosphorylation, but increased NeuN, BCL-2 expressions for AD rats. Notably, Crocin increased the α and β diversity of the IM in AD rats. However, DKK3 overexpression reversed these situations. Additionally, Crocin treatment led to an increase in Prevotellaceae_NK3B31_group, alongside reductions in Lachnospiraceae UCG-001 and Family_XIII_AD3011_group.

Conclusion

Crocin alleviated AD by regulating DKK3-mediated IM variation, suggesting that DKK3-mediated IM variation was a potential therapeutic target for AD.

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.