Research Paper Volume 12, Issue 1 pp 628—649
Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice
- 1 General Practice Department, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China
- 2 Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
- 3 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
- 4 Department of Geriatrics, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China
Received: November 6, 2019 Accepted: December 23, 2019 Published: January 6, 2020
https://doi.org/10.18632/aging.102645How to Cite
Abstract
Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer’s disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels in the plasma of choline-treated APP/PS1 mice (an AD mouse model) with and without probiotic treatments. We found that declines in L. plantarum in the gut were associated with cognitive impairment. Moreover, 12-weeks of treatment with memantine plus L. plantarum ameliorated cognitive deterioration, decreased Αβ levels in the hippocampus, and protected neuronal integrity and plasticity. These effects were accompanied by reductions in TMAO synthesis and neuroinflammation. These experiments demonstrate that L. plantarum augments the beneficial therapeutic effects of memantine treatment in APP/PS1 mice by remodeling the intestinal microbiota, inhibiting the synthesis of TMAO, and reducing clusterin levels. Our results thus highlight intestinal microbiota as a potential therapeutic target to decrease the risk of AD.
Abbreviations
AD: Alzheimer’s disease; ANOVA: One-way analysis of variance; APP: Amyloid precursor protein; AUC: Area under the curve; Aβ: Amyloid-β; L. plantarum: Lactobacillus plantarum; FMOs: Flavin monooxygenases; G-CSF: Granulocyte colony-stimulating factor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IFNγ: Interferon-γ; IL: Interleukin; IP: Interferon-induced protein; LTP: Long-term potentiation; MCP-1: Monocyte chemotactic protein-1; MIP-1β: Macrophage inflammatory protein-1β; PC: Principal components; PCA: Principal component analysis; RANTES: Regulated upon activation normal T cell expressed and secreted factor; ROC: Receiver operating characteristic; TMA: Trimethylamine; TMAO: Trimethylamine-N-oxide; TNF: Tumor necrosis factor; WT: Wild type.