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:

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.

• 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
• Journal: BMC complementary medicine and therapies (BMC Complement Med Ther) Vol. 21 Issue 1 Pg. 259 (Oct 09 2021) ISSN: 2662-7671 [Electronic] England
• PMID: 34627204 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Neuroprotective Agents
• Propionates
• Streptozocin
• Glycogen Synthase Kinase 3 beta
• propionic acid

Topics

• Alzheimer Disease
• Animals
• Cognitive Dysfunction (prevention & control)
• Disease Models, Animal
• Gliosis (metabolism)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Lactobacillus plantarum (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Neuroprotective Agents (pharmacology)
• Propionates (metabolism)
• Streptozocin (administration & dosage)