Potential Therapeutic Effects of Bifidobacterium breve MCC1274 on Alzheimer's Disease Pathologies in AppNL-G-F Mice

Mona Abdelhamid; Cha-Gyun Jung; Chunyu Zhou; Rieko Inoue; Yuxin Chen; Yoshiki Sento; Hideki Hida; Makoto Michikawa

doi:10.3390/nu16040538

Potential Therapeutic Effects of Bifidobacterium breve MCC1274 on Alzheimer's Disease Pathologies in App^NL-G-F Mice

Nutrients. 2024 Feb 15;16(4):538. doi: 10.3390/nu16040538.

Authors

Mona Abdelhamid¹, Cha-Gyun Jung^{1

2}, Chunyu Zhou¹, Rieko Inoue¹, Yuxin Chen¹, Yoshiki Sento³, Hideki Hida², Makoto Michikawa^{1

4}

Affiliations

¹ Department of Biochemistry, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
² Department of Neurophysiology and Brain Science, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
³ Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
⁴ Department of Geriatric Medicine School of Life, Dentistry at Niigata, Nippon Dental University, 1-8 Hamaura-cho, Chuo-ku, Niigata 951-8580, Japan.

Abstract

We previously demonstrated that orally supplemented Bifidobacterium breve MCC1274 (B. breve MCC1274) mitigated Alzheimer's disease (AD) pathologies in both 7-month-old App^NL-G-F mice and wild-type mice; thus, B. breve MCC1274 supplementation might potentially prevent the progression of AD. However, the possibility of using this probiotic as a treatment for AD remains unclear. Thus, we investigated the potential therapeutic effects of this probiotic on AD using 17-month-old App^NL-G-F mice with memory deficits and amyloid beta saturation in the brain. B. breve MCC1274 supplementation ameliorated memory impairment via an amyloid-cascade-independent pathway. It reduced hippocampal and cortical levels of phosphorylated extracellular signal-regulated kinase and c-Jun N-terminal kinase as well as heat shock protein 90, which might have suppressed tau hyperphosphorylation and chronic stress. Moreover, B. breve MCC1274 supplementation increased hippocampal synaptic protein levels and upregulated neuronal activity. Thus, B. breve MCC1274 supplementation may alleviate cognitive dysfunction by reducing chronic stress and tau hyperphosphorylation, thereby enhancing both synaptic density and neuronal activity in 17-month-old App^NL-G-F mice. Overall, this study suggests that B. breve MCC1274 has anti-AD effects and can be used as a potential treatment for AD.

Keywords: Alzheimer’s disease; Bifidobacterium breve MCC1274; c-Jun N-terminal kinase; cognitive dysfunction; extracellular signal-regulated kinase; glial activation; synapses; tau phosphorylation.

MeSH terms

Alzheimer Disease* / metabolism
Amyloid beta-Peptides / metabolism
Amyloid beta-Protein Precursor / genetics
Amyloid beta-Protein Precursor / metabolism
Animals
Bifidobacterium breve* / metabolism
Disease Models, Animal
Memory Disorders / drug therapy
Mice
Mice, Transgenic
Mobile Applications*

Substances

Amyloid beta-Peptides
Amyloid beta-Protein Precursor

Grants and funding

This research was funded by a grant-in-aid of the 24th General Assembly of the Japanese Association of Medical Sciences JOSE205048 (to C.-G.J.), by the Grant-in-Aid for Scientific Research C 20K07762 (to C.-G.J.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and by AMED under Grant Number JP20dk0207050h001 and Grant Number JP20de010702 (to M.M.).