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BMC Complementary Medicine and Therapies

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01-12-2021 | Alzheimer's Disease | Research article

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

Authors: 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

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

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.

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Title: Lactobacillus plantarum PS128 prevents cognitive dysfunction in Alzheimer’s disease mice by modulating propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis
Authors: 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
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Alzheimer's Disease
Alzheimer's Disease
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03426-8

Keynote webinar | Spotlight on medication adherence

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

Abstract

Background

Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objectives

Methods

Results

Conclusions

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Other articles of this Issue 1/2021

In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

Three chemotypes of thyme (Thymus vulgaris L.) essential oil and their main compounds affect differently the IL-6 and TNFα cytokine secretions of BV-2 microglia by modulating the NF-κB and C/EBPβ signalling pathways

Use of complementary and alternative therapies by patients with eye diseases: a hospital-based cross-sectional study from Palestine

Use of complementary and alternative medicine in Norway: a cross-sectional survey with a modified Norwegian version of the international questionnaire to measure use of complementary and alternative medicine (I-CAM-QN)

Activity of antifungal drugs and Brazilian red and green propolis extracted with different methodologies against oral isolates of Candida spp.

Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea