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Food Microbiology and Biotechnology

Probiotic Mixture KF Attenuates Age-Dependent Memory Deficit and Lipidemia in Fischer 344 Rats

Jin-Ju Jeong 1, Kyung-Ah Kim 1, Young-Tae Ahn 2, Jae-Hun Sim 2, Jae-Yeon Woo 1, Chul-Sung Huh 3 and Dong-Hyun Kim 1*

1Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea, 2R&BD Center, Korea Yakult Co., Ltd., Yongin 449-901, Republic of Korea, 3Graduate School of International Agricultural Technology/GBST, Seoul National University, Gangwon 232-916, Republic of Korea

Received: May 6, 2015; Accepted: May 14, 2015

J. Microbiol. Biotechnol. 2015; 25(9): 1532-1536

Published September 28, 2015 https://doi.org/10.4014/jmb.1505.05002

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

To investigate the memory-enhancing effect of lactic acid bacteria, we selected the probiotic mixture KF, which consisted of Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 (1 × 1011 CFU/g of each strain), and investigated its antilipidemic and memoryenhancing effects in aged Fischer 344 rats. KF (1 × 1010 CFU/rat/day), which was administered orally once a day (6 days per week) for 8 weeks, significantly inhibited age-dependent increases of blood triglyceride and reductions of HDL cholesterol (p < 0.05). KF restored agereduced spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats (p < 0.05). KF treatment slightly, but not significantly, shortened the escape latency daily for 4 days. Oral administration of KF restored age-suppressed doublecortin and brain-derived neurotrophic factor expression in aged rats. Orally administered KF suppressed the expression of p16, p53, and cyclooxygenase-2, the phosphorylation of Akt and mTOR, and the activation of NF-κB in the hippocampus of the brain. These findings suggest that KF may ameliorate age-dependent memory deficit and lipidemia by inhibiting NF-κB activation.

Keywords

aging, memory deficit, lipidemia, Lactobacillus plantarum, Lactobacillus curvatus

References

  1. Bubici C, Papa S, Dean K, Franzoso G. 2006. Mutual crosstalk between reactive oxygen species and nuclear factorkappa B: molecular basis and biological significance. Oncogene 25: 6731-6748.
    Pubmed CrossRef
  2. Cammarota G, Ianiro G, Bibbò S, Gasbarrini A. 2014. Gut microbiota modulation: probiotics, antibiotics or fecal microbiota transplantation? Intern. Emerg. Med. 9: 365-373.
    Pubmed CrossRef
  3. Chapple IL. 1997. Reactive oxygen species and antioxidants in inflammatory diseases. J. Clin. Periodontol. 24: 287-296
    Pubmed CrossRef
  4. Chung H, Lee E, Choi Y, Kim J, Kim D, Zou Y, et al. 2011. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J. Dent. Res. 90: 830840.
    Pubmed CrossRef
  5. Craft S. 2005. Insulin resistance syndrome and Alzheimer’s disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol. Aging 26: 65-69.
    Pubmed CrossRef
  6. Fitzgerald PJ, Seemann JR, Maren S. 2014. Can fear extinction be enhanced? A review of pharmacological and behavioral findings. Brain Res. Bull. 105: 46-60
    Pubmed PMC CrossRef
  7. Hirsch E, Breidert T, Rousselet E, Hunot S, Hartmann A, Michel P. 2003. The role of glial reaction and inflammation in Parkinson’s disease. Ann. NY Acad. Sci. 991: 214-228.
    Pubmed CrossRef
  8. Jang SE, Hyam SR, Han MJ, Kim SY, Lee BG, Kim DH. 2013. Lactobacillus brevis G-101 ameliorates colitis in mice by inhibiting NF-κB, MAPK and AKT pathways and by polarizing M1 macrophages to M2-like macrophages. J. Appl. Microbiol. 115: 888-896.
    Pubmed CrossRef
  9. Jeong JJ, Kim KA, Jang SE, Woo JY, Han MJ, Kim DH. 2015. Orally administrated Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent colitis by inhibiting the nuclear factor-kappa B signaling pathway via the regulation of lipopolysaccharide production by gut microbiota. PLoS One 10: e0116533.
    Pubmed PMC CrossRef
  10. Luine V, Frankfurt M. 2013. Interactions between estradiol, BDNF and dendritic spines in promoting memory. Neuroscience 239: 34-45.
    Pubmed PMC CrossRef
  11. McGeer PL, McGeer EG. 2004. Inflammation and the degenerative diseases of aging. Ann. NY Acad. Sci. 1035:104-116.
    Pubmed CrossRef
  12. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr CR, Kawas CH, et al. 2011. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer Dement. 7: 263-269.
    Pubmed PMC CrossRef
  13. Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, et al. 2013. Proinflammatory cytokines, aging, and age-related diseases. J. Am. Med. Dir. Assoc. 14: 877-882.
    Pubmed CrossRef
  14. Morelli L. 2014. Yogurt, living cultures, and gut health. Am. J. Clin. Nutr. 99: 1248S-1250S.
    Pubmed CrossRef
  15. Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schröder S, Adler T, et al. 2013. Rapamycin extends murine lifespan but has limited effects on aging. J. Clin. Invest. 123: 32723291.
    Pubmed PMC CrossRef
  16. Park DY, A hn YT, Park SH, H uh C S, Y oo SR, Yu R , et al. 2013. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One 8: e59470.
    Pubmed PMC CrossRef
  17. Peterson CT, Sharma V, Elmén L, Peterson SN. 2015. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clin. Exp. Immunol. 179: 363-377
    Pubmed PMC CrossRef
  18. Sarter M, Bruno JP. 2004. Developmental origins of the agerelated decline in cortical cholinergic function and associated cognitive abilities. Neurobiol. Aging 25: 1127-1139.
    Pubmed CrossRef
  19. Terry AV, Buccafusco JJ. 2003. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Therap. 306: 821-827.
    Pubmed CrossRef
  20. Woo JY, Gu W, Kim KA, Jang SE, Han MJ, Kim DH. 2014. Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model. Anaerobe 27: 22-26.
    Pubmed CrossRef
  21. Yu BP, Yang R. 1996. Critical evaluation of the free radical theory of aging. Ann. NY Acad. Sci. 786: 1-11.
    Pubmed CrossRef

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Article

Note

J. Microbiol. Biotechnol. 2015; 25(9): 1532-1536

Published online September 28, 2015 https://doi.org/10.4014/jmb.1505.05002

Copyright © The Korean Society for Microbiology and Biotechnology.

Probiotic Mixture KF Attenuates Age-Dependent Memory Deficit and Lipidemia in Fischer 344 Rats

Jin-Ju Jeong 1, Kyung-Ah Kim 1, Young-Tae Ahn 2, Jae-Hun Sim 2, Jae-Yeon Woo 1, Chul-Sung Huh 3 and Dong-Hyun Kim 1*

1Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea, 2R&BD Center, Korea Yakult Co., Ltd., Yongin 449-901, Republic of Korea, 3Graduate School of International Agricultural Technology/GBST, Seoul National University, Gangwon 232-916, Republic of Korea

Received: May 6, 2015; Accepted: May 14, 2015

Abstract

To investigate the memory-enhancing effect of lactic acid bacteria, we selected the probiotic
mixture KF, which consisted of Lactobacillus plantarum KY1032 and Lactobacillus curvatus
HY7601 (1 × 1011 CFU/g of each strain), and investigated its antilipidemic and memoryenhancing
effects in aged Fischer 344 rats. KF (1 × 1010 CFU/rat/day), which was administered
orally once a day (6 days per week) for 8 weeks, significantly inhibited age-dependent
increases of blood triglyceride and reductions of HDL cholesterol (p < 0.05). KF restored agereduced
spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats
(p < 0.05). KF treatment slightly, but not significantly, shortened the escape latency daily for 4
days. Oral administration of KF restored age-suppressed doublecortin and brain-derived
neurotrophic factor expression in aged rats. Orally administered KF suppressed the
expression of p16, p53, and cyclooxygenase-2, the phosphorylation of Akt and mTOR, and the
activation of NF-κB in the hippocampus of the brain. These findings suggest that KF may
ameliorate age-dependent memory deficit and lipidemia by inhibiting NF-κB activation.

Keywords: aging, memory deficit, lipidemia, Lactobacillus plantarum, Lactobacillus curvatus

References

  1. Bubici C, Papa S, Dean K, Franzoso G. 2006. Mutual crosstalk between reactive oxygen species and nuclear factorkappa B: molecular basis and biological significance. Oncogene 25: 6731-6748.
    Pubmed CrossRef
  2. Cammarota G, Ianiro G, Bibbò S, Gasbarrini A. 2014. Gut microbiota modulation: probiotics, antibiotics or fecal microbiota transplantation? Intern. Emerg. Med. 9: 365-373.
    Pubmed CrossRef
  3. Chapple IL. 1997. Reactive oxygen species and antioxidants in inflammatory diseases. J. Clin. Periodontol. 24: 287-296
    Pubmed CrossRef
  4. Chung H, Lee E, Choi Y, Kim J, Kim D, Zou Y, et al. 2011. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J. Dent. Res. 90: 830840.
    Pubmed CrossRef
  5. Craft S. 2005. Insulin resistance syndrome and Alzheimer’s disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol. Aging 26: 65-69.
    Pubmed CrossRef
  6. Fitzgerald PJ, Seemann JR, Maren S. 2014. Can fear extinction be enhanced? A review of pharmacological and behavioral findings. Brain Res. Bull. 105: 46-60
    Pubmed KoreaMed CrossRef
  7. Hirsch E, Breidert T, Rousselet E, Hunot S, Hartmann A, Michel P. 2003. The role of glial reaction and inflammation in Parkinson’s disease. Ann. NY Acad. Sci. 991: 214-228.
    Pubmed CrossRef
  8. Jang SE, Hyam SR, Han MJ, Kim SY, Lee BG, Kim DH. 2013. Lactobacillus brevis G-101 ameliorates colitis in mice by inhibiting NF-κB, MAPK and AKT pathways and by polarizing M1 macrophages to M2-like macrophages. J. Appl. Microbiol. 115: 888-896.
    Pubmed CrossRef
  9. Jeong JJ, Kim KA, Jang SE, Woo JY, Han MJ, Kim DH. 2015. Orally administrated Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent colitis by inhibiting the nuclear factor-kappa B signaling pathway via the regulation of lipopolysaccharide production by gut microbiota. PLoS One 10: e0116533.
    Pubmed KoreaMed CrossRef
  10. Luine V, Frankfurt M. 2013. Interactions between estradiol, BDNF and dendritic spines in promoting memory. Neuroscience 239: 34-45.
    Pubmed KoreaMed CrossRef
  11. McGeer PL, McGeer EG. 2004. Inflammation and the degenerative diseases of aging. Ann. NY Acad. Sci. 1035:104-116.
    Pubmed CrossRef
  12. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr CR, Kawas CH, et al. 2011. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer Dement. 7: 263-269.
    Pubmed KoreaMed CrossRef
  13. Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, et al. 2013. Proinflammatory cytokines, aging, and age-related diseases. J. Am. Med. Dir. Assoc. 14: 877-882.
    Pubmed CrossRef
  14. Morelli L. 2014. Yogurt, living cultures, and gut health. Am. J. Clin. Nutr. 99: 1248S-1250S.
    Pubmed CrossRef
  15. Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schröder S, Adler T, et al. 2013. Rapamycin extends murine lifespan but has limited effects on aging. J. Clin. Invest. 123: 32723291.
    Pubmed KoreaMed CrossRef
  16. Park DY, A hn YT, Park SH, H uh C S, Y oo SR, Yu R , et al. 2013. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One 8: e59470.
    Pubmed KoreaMed CrossRef
  17. Peterson CT, Sharma V, Elmén L, Peterson SN. 2015. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clin. Exp. Immunol. 179: 363-377
    Pubmed KoreaMed CrossRef
  18. Sarter M, Bruno JP. 2004. Developmental origins of the agerelated decline in cortical cholinergic function and associated cognitive abilities. Neurobiol. Aging 25: 1127-1139.
    Pubmed CrossRef
  19. Terry AV, Buccafusco JJ. 2003. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Therap. 306: 821-827.
    Pubmed CrossRef
  20. Woo JY, Gu W, Kim KA, Jang SE, Han MJ, Kim DH. 2014. Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model. Anaerobe 27: 22-26.
    Pubmed CrossRef
  21. Yu BP, Yang R. 1996. Critical evaluation of the free radical theory of aging. Ann. NY Acad. Sci. 786: 1-11.
    Pubmed CrossRef