Lactobacillus plantarum PS128 prevents cognitive dysfunction in Alzheimer’s disease mice by modulating propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis

Hei Jen Huang, Jie Ling Chen, Jian Fu Liao, Yu Hsin Chen, Min Wei Chieu, Ya Yun Ke, Chih Chieh Hsu, Ying Chieh Tsai, Hsiu Mei Hsieh-Li*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

摘要

Background: According to recent evidence, psychobiotics exert beneficial effects on central nervous system-related diseases, such as mental disorders. Lactobacillus plantarum PS128 (PS128), a novel psychobiotic strain, improves motor function, depression, and anxiety behaviors. However, the psychobiotic effects and mechanisms of PS128 in Alzheimer’s disease (AD) remain to be explored. Objectives: The goal of the current study was to evaluate the beneficial effects of PS128 and to further elucidate its mechanism in AD mice. Methods: PS128 (1010 colony-forming unit (CFU)/ml) was administered via oral gavage (o.g.) to 6-month-old male wild-type B6 and 3 × Tg-AD mice (harboring the PS1M146V, APPswe and TauP30IL transgenes) that received an intracerebroventricular injection of streptozotocin (icv-STZ, 3 mg/kg) or vehicle (saline) for 33 days. After serial behavioral tests, fecal short-chain fatty acid levels and AD-related pathology were assessed in these mice. Results: Our findings show that intracerebroventricular injection of streptozotocin accelerated cognitive dysfunction associated with increasing levels of glycogen synthase kinase 3 beta (GSK3β) activity, tau protein phosphorylation at the T231 site (pT231), amyloid-β (Aβ) deposition, amyloid-β protein precursor (AβPP), β-site AβPP-cleaving enzyme (BACE1), gliosis, fecal propionic acid (PPA) levels and cognition-related neuronal loss and decreasing postsynaptic density protein 95 (PSD95) levels in 3 × Tg-AD mice. PS128 supplementation effectively prevented the damage induced by intracerebroventricular injection of streptozotocin in 3 × Tg-AD mice. Conclusions: Based on the experimental results, intracerebroventricular injection of streptozotocin accelerates the progression of AD in the 3 × Tg-AD mice, primarily by increasing the levels of gliosis, which were mediated by the propionic acid and glycogen synthase kinase 3 beta pathways. PS128 supplementation prevents damage induced by intracerebroventricular injection of streptozotocin by regulating the propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis in 3 × Tg-AD mice. Therefore, we suggest that PS128 supplementation is a potential strategy to prevent and/or delay the progression of AD.

原文英語
文章編號259
期刊BMC Complementary Medicine and Therapies
21
發行號1
DOIs
出版狀態已發佈 - 2021 十二月

ASJC Scopus subject areas

  • 補充和替代醫學

指紋

深入研究「Lactobacillus plantarum PS128 prevents cognitive dysfunction in Alzheimer’s disease mice by modulating propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis」主題。共同形成了獨特的指紋。

引用此