Heat-Inactivated Bifidobacterium longum Z1 Improves Recognition Memory in Mice in Association with Enhanced Trk-CREB Signaling and Reduced Methylglyoxal Levels
5 affiliations
- 1Division of Food Science and Technology and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju-si 52828, Republic of Korea
- 2Functional Food Research Institute, Industry-University Cooperation Foundation, Daegu Haany University, Gyeongsan-si 38610, Republic of Korea
- 3Department of Food Industry, Daegu Haany University, Gyeongsan-si 38610, Republic of Korea
- 4Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
- 5College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Republic of Korea
Abstract
Probiotics can modulate brain function via the microbiota–gut–brain axis; however, their cognitive effects in healthy hosts and the underlying pathways remain unclear. We previously reported that Bifidobacterium longum Z1 protects neuronal cells against methylglyoxal (MGO)-induced glycotoxicity. Here, we investigated whether oral heat-inactivated B. longum Z1 enhances memory in normal mice and examined associated molecular changes. Male C57BL/6 mice received heat-inactivated B. longum Z1 (5 or 20 mg/kg/day) or piracetam (400 mg/kg/day) for seven days before behavioral testing. High-dose B. longum Z1 (High-Z1) significantly increased the recognition index in the novel object recognition test. In exploratory brain analyses of mice selected by recognition index, High-Z1 increased the level of a nerve growth factor-immunoreactive band and the phosphorylation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding protein (CREB), whereas TrkA phosphorylation was not significantly changed. High-Z1 reduced MGO levels in the liver, brain, and serum, and in a separate exploratory cohort, a higher dose (100 mg/kg) upregulated hepatic glyoxalase-I and II and increased nuclear levels of nuclear factor erythroid 2-related factor-2 (Nrf-2). These molecular changes are associative and do not establish that neurotrophin-Trk-CREB signaling, the glyoxalase pathway, or MGO reduction mediates the behavioral effect. These findings support further investigation of this heat-inactivated B. longum Z1 preparation as a postbiotic for cognitive health.
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BibTeX
@article{hong2026heatinactivated,
title = {{Heat-Inactivated Bifidobacterium longum Z1 Improves Recognition Memory in Mice in Association with Enhanced Trk-CREB Signaling and Reduced Methylglyoxal Levels}},
author = {Seong-Min Hong and Jaehoon Bae and Seojin Kang and Hyunjin Kang and Dong-Hyun Kim and Sun Yeou Kim},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110054},
url = {https://www.mdpi.com/1422-0067/27/21/10054},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Heat-Inactivated Bifidobacterium longum Z1 Improves Recognition Memory in Mice in Association with Enhanced Trk-CREB Signaling and Reduced Methylglyoxal Levels
AU - Seong-Min Hong
AU - Jaehoon Bae
AU - Seojin Kang
AU - Hyunjin Kang
AU - Dong-Hyun Kim
AU - Sun Yeou Kim
PY - 2026
DA - 2026/11/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110054
UR - https://www.mdpi.com/1422-0067/27/21/10054
AB - Probiotics can modulate brain function via the microbiota–gut–brain axis; however, their cognitive effects in healthy hosts and the underlying pathways remain unclear. We previously reported that Bifidobacterium longum Z1 protects neuronal cells against methylglyoxal (MGO)-induced glycotoxicity. Here, we investigated whether oral heat-inactivated B. longum Z1 enhances memory in normal mice and examined associated molecular changes. Male C57BL/6 mice received heat-inactivated B. longum Z1 (5 or 20 mg/kg/day) or piracetam (400 mg/kg/day) for seven days before behavioral testing. High-dose B. longum Z1 (High-Z1) significantly increased the recognition index in the novel object recognition test. In exploratory brain analyses of mice selected by recognition index, High-Z1 increased the level of a nerve growth factor-immunoreactive band and the phosphorylation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding protein (CREB), whereas TrkA phosphorylation was not significantly changed. High-Z1 reduced MGO levels in the liver, brain, and serum, and in a separate exploratory cohort, a higher dose (100 mg/kg) upregulated hepatic glyoxalase-I and II and increased nuclear levels of nuclear factor erythroid 2-related factor-2 (Nrf-2). These molecular changes are associative and do not establish that neurotrophin-Trk-CREB signaling, the glyoxalase pathway, or MGO reduction mediates the behavioral effect. These findings support further investigation of this heat-inactivated B. longum Z1 preparation as a postbiotic for cognitive health.
SN - 1422-0067
ER -