Ameliorative effects of Akkermansia muciniphila on anxiety-like behavior and cognitive deficits in a rat model of Alzheimer’s disease

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2024-10-16 DOI:10.1016/j.brainres.2024.149280

Hamideh Maftoon , Seyed Davar Siadat , Samira Tarashi , Erfan Soroush , Mohammad Basir Asefi , Abbas Rahimi Foroushani , Mohammad Mehdi Soltan Dallal

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Abstract

Alzheimer’s Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic–pituitary–adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores Akkermansia muciniphila’s impact on preventing AD. This research investigates the effect of A. muciniphila consumption (1 × 10⁹ CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with A. muciniphila). A. muciniphila gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of A. muciniphila treatment, anxiety-like behavior significantly decreased. The AD group receiving A. muciniphila showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ) decreased. A. muciniphila effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis.

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Akkermansia muciniphila 对阿尔茨海默病大鼠模型中焦虑样行为和认知缺陷的改善作用

阿尔茨海默病（AD）是老年人主要的神经退行性疾病，目前尚无确切的治疗方法。肠道微生物群通过帮助下丘脑-垂体-肾上腺（HPA）轴的发育和神经调节剂的产生来影响肠道-大脑轴。研究将注意力缺失症与肠道微生物群联系起来，表明肠道微生物群调节可能是注意力缺失症的一种治疗方法。本研究探讨了 Akkermansia muciniphila 对预防注意力缺失症的影响。与对照组相比，本研究调查了食用 A. muciniphila（1 × 109 CFU）对 tau 蛋白诱导的 AD 大鼠的影响。大鼠被分为四组：假组、假+Akk组、AD组（tau诱导的大鼠）和AD+Akk组（用粘蛋白噬菌体治疗tau诱导的大鼠）。灌胃 A. muciniphila 持续五周。对大鼠进行qRT-PCR分析，以评估海马中促炎因子（TNF-α、IL-6、IL-1β、IFN-γ）的mRNA表达。行为测试包括莫里斯水迷宫（MWM）、被动回避记忆测试（穿梭箱）、高架正迷宫（EPM）和大理石埋藏。经过五周的A. muciniphila治疗后，焦虑样行为明显减少。与AD组相比，接受A. muciniphila治疗的AD组的空间记忆和识别记忆有所改善。促炎细胞因子水平（TNF-α、IL-1β、IL-6、IFN-γ）下降。A.muciniphila能有效减少认知障碍和焦虑相关行为，通过影响肠道-大脑轴，有望成为一种AD疗法。

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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.