Kefir peptides exhibit antidepressant-like activity in mice through the BDNF/TrkB pathway |
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| Authors: | Hsiao-Ling Chen Ying-Wei Lan Min-Yu Tu Yu-Tang Tung Megan Ning-Yu Chan Hsin-Shan Wu Chih-Ching Yen Chuan-Mu Chen |
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| Affiliation: | 1. Department of Biomedical Sciences, Da-Yeh University, Changhwa 515, Taiwan;2. Department of Life Sciences, and PhD Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan;3. Department of Health Business Administration, Meiho University, Pingtung 912, Taiwan;4. Aviation Physiology Research Laboratory, Kaohsiung Armed Forces General Hospital Gangshan Branch, Kaohsiung 820, Taiwan;5. Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan;6. Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 110, Taiwan;7. Division of Structural Biology and Biochemistry, Nanyang Technological University, Singapore 639798, Singapore;8. Department of Internal Medicine, China Medical University Hospital, and College of Health Care, China Medical University, Taichung 404, Taiwan;9. The iEGG and Animal Biotechnology Center, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan |
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| Abstract: | Depression is a prevalent, stress-related mental disorder that can lead to serious psychiatric diseases with morbidity and high mortality. Although some functional fermented dairy drinks have promising anxiolytic and antidepressant effects, the mechanism is still not clear. To determine the antidepressant-like effect and the potential molecule mechanism of kefir peptides (KP), various behavioral tests, including the elevated plus maze test, open field test, forced swimming test, and tail suspension test, were used. Administration of 150 mg/kg KP in mice reduced the duration of immobility in the forced swimming test and tail suspension test, elevated the time spent in the open arm and center zone in the elevated plus maze test, and increased the total distance traveled, average speed, and time spent in the center zone in the open field test compared with the mock group. These results indicated that KP dramatically ameliorated the depression-like behaviors. Kefir peptides were further isolated and identified using high-performance liquid chromatography and liquid chromatography–tandem mass spectrometry, from which 3 peptides were identified and designated KFP-1, KFP-3, and KFP-5. Among these peptides, administration of KFP-3 (15 AA residues) remarkably decreased immobility time in the forced swimming test and increased mobility time in the tail suspension test. Therefore, KFP-3 may be the major active peptide with antidepressant activity in KP. Overexpression of brain-derived neurotrophic factor, phosphorylated tropomyosin receptor kinase B, and phosphorylated ERK1/2 protein levels could be detected in the hippocampus under KP administration. Therefore, we suggest that KP improves depressive-like behaviors by activating the brain-derived neurotrophic factor–phosphorylated tropomyosin receptor kinase B signaling pathway. Kefir peptides may serve as a new type of antidepressant dairy product and may provide potent antidepressant effects for clinical use. |
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| Keywords: | kefir peptide depressive-like behavior brain-derived neurotrophy factor tropomyosin receptor kinase B extracellular signal-regulated kinase 1/2 |
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