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痤疮丙酸杆菌通过与微管相关的结构变化诱导 wistar 大鼠大脑产生类似阿尔茨海默病的病理。

Cutibacterium Acnes induces Alzheimer's disease-like pathology in brains of wistar rats through structural changes associated with microtubules.

机构信息

Department of Cognitive Neuroscience, Institute for Cognitive Science Studies, Tehran, 1658344575, Iran.

Cognitive and Neuroscience Research Center, Amir-Almomenin Hospital, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.

出版信息

Behav Brain Funct. 2024 Nov 21;20(1):30. doi: 10.1186/s12993-024-00257-8.

Abstract

BACKGROUND

Cutibacterium acnes(C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer's disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons.

METHODS

In this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated.

RESULTS

C. acnes-infected rats displayed memory deficits and Aβ deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals.

CONCLUSION

Based on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites.

摘要

背景

痤疮丙酸杆菌(C. acnes)是一种革兰氏阳性厌氧菌,也是面部皮脂腺毛囊中的优势细菌种类,在阿尔茨海默病(AD)患者的大脑中被检测到。现已发现 C. acnes 通过产生促炎细胞因子非特异性激活固有免疫系统,并能参与脑炎症反应。我们假设 C. acnes 可以通过改变神经元轴突和树突的结构来影响大脑。

方法

在这方面,我们用 C. acnes 感染大鼠的海马组织,研究感染后大鼠的记忆保留情况、海马组织中的淀粉样β(Aβ)沉积、过度磷酸化的 tau 蛋白(p-Tau)形成以及海马组织中 MAP2 和 β-微管蛋白蛋白的表达水平。

结果

感染 C. acnes 的大鼠表现出记忆缺陷,并且在感染后 7 天内其海马组织中检测到 Aβ 沉积。C. acnes 具有神经毒性,并对 MAP2 和 β-微管蛋白等正常神经元功能所必需的蛋白产生有害影响。在感染动物中还发现 p-Tau 水平升高。

结论

基于这些结果,我们提出 C. acnes 对大脑的感染通过轴突和树突的退化参与了散发性 AD 的发病机制的启动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3269/11583404/d1bcf34def3e/12993_2024_257_Fig1_HTML.jpg

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