Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl₃ induced mouse model of Alzheimer’s disease via modulating gut microbiota and PI3K/Akt/GSK-3β signaling pathway

ABSTRACT

Probiotic intervention has beneficial effects on host brain function and behavior via regulating microbiota-gut-brain axis; however, the underlying mechanism is not yet understood. Herein, we investigated that the effects of Lactobacillus plantarum DP189 (DP189) administration in preventing cognitive dysfunction and pathology of Alzheimer’s disease (AD) in D-galactose (D-gal) and AlCl₃-induced AD model mice. After L. plantarum DP189 intervention for 10 weeks, we assessed cognitive behavior, neurotransmitter expression, histological changes, microbial communities, and the mechanisms underlying the disease in AD model mice. The results showed that L. plantarum DP189 intervention prevented cognitive dysfunction by behavioral test. Increased levels of serotonin, dopamine, and gamma-aminobutyric acid positively affected the pathological processes by ameliorating neuronal damage, beta-amyloid deposition, and tau pathology. L. plantarum DP189 intervention simultaneously modulated the gut microbial communities to alleviate gut dysbiosis. Moreover, L. plantarum DP189 inhibited tau hyperphosphorylation by regulating the PI3 K/Akt/GSK-3β pathway. These findings indicated that L. plantarum DP189 intervention is a promising therapeutic strategy to prevent the onset and development of AD.

KEYWORDS:

• Lactobacillus plantarum
• Alzheimer’s disease
• gut microbiota
• GSK-3β
• PI3K
• microbiota-gut-brain axis
• cognitive dysfunction
• probiotics

Data availability

The gene sequencing data for this study can be found on National Center for Biotechnology Information (NCBI) accession number PRJNA720795.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

All experiments were conducted in accordance with the guidelines of the Animal Care Committee of Jilin Academy of Agricultural Sciences, and all procedures were approved by the local Animal Ethics Committee.

Additional information

Funding

This work was financially supported by Basic Scientific Research Projects of Jilin Academy of Agricultural Sciences (KYJF2021ZR016), China Agriculture Research System of MOF and MARA, Agricultural Science and Technology Innovation Program of Jilin Province (C02100308), Key Research and Development Program of Liaoning Provence (2019JH2/10300010), and 2018 Funding Plan for Introducing High-level Scientific and Technological Innovation Talents to Jilin scientific research institutes (2060399).

Notes on contributors

Xinping Song

Xinping Song master candidate in Food science and Engineering from Yanbian University.

Zijian Zhao

Zijian Zhao received his Ph.D. in Physical Chemistry from Jilin University, and is research assistant in Jilin Academy of Agricultural Sciences.

Yujuan Zhao

Yujuan Zhao received her M.Sc. in Agriculture from Jilin Agricultural University, and is associate professor in Jilin Academy of Agricultural Sciences.

Zhiguo Wang

Zhiguo Wang received his master degree in Software Engineering from Jilin University, and is a director technologist with the Department of Nuclear Medicine, Northern Theater Command, PLA, and is associate professor with Northeastern University, China Medical University, Dalian Medical University and Jinzhou Medical University.

Chao Wang

Chao Wang recevied her M.Sc. in Food Science in Northeast Agricultural University, and is associate professor in Jilin Academy of Agricultural Sciences.

Ge Yang

Ge Yang received his M.Sc. in Science of Chinese Pharmacology from Jilin Agricultural University, and is research assistant in Jilin Academy of Agricultural Sciences.

Shengyu Li

Shengyu Li recevied his Ph.D. in Biochemistry and Molecular Biology from Northeast Normal University, and is professor in Jilin Academy of Agricultural Sciences.