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Prolyl‐hydroxyproline, a collagen‐derived dipeptide, enhances hippocampal cell proliferation, which leads to antidepressant‐like effects in mice
Author(s) -
Nogimura Dai,
Mizushige Takafumi,
Taga Yuki,
Nagai Akitoshi,
Shoji Sayo,
Azuma Nao,
Kusubata Masashi,
Adachi Shinichi,
Yoshizawa Fumiaki,
Kabuyama Yukihito
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902871r
Subject(s) - neurotrophic factors , hydroxyproline , antidepressant , endocrinology , pharmacology , brain derived neurotrophic factor , hippocampal formation , oral administration , hippocampus , medicine , chemistry , progenitor cell , in vivo , behavioural despair test , stem cell , microbiology and biotechnology , biology , receptor
Depression has been a mental health issue worldwide. We previously reported that ginger‐degraded collagen hydrolysate (GDCH) suppressed depression‐like behavior in mice. Furthermore, prolyl‐hydroxyproline (PO) and hydroxyprolyl‐glycine (OG) were detected in the circulating blood after the oral administration of GDCH. In the present study, PO, but not OG, was detected in the cerebrospinal fluid of rats after the oral administration of GDCH, suggesting that PO is transported from blood to the brain. We then investigated the effects of PO and OG on the depression‐like behavior of mice. The oral administration of PO significantly decreased depression‐like behavior in the forced swim test. OG had no antidepressant‐like effect. In addition, proline and hydroxyproline, components of PO, also had no antidepressant‐like effect after their oral administration. PO significantly increased the gene expression of brain‐derived neurotrophic factor and nerve growth factor in the hippocampus, and promoted the proliferation of neural progenitor cells in vivo and in vitro. PO also increased the dopamine concentration in the prefrontal cortex. Thus, PO‐dependent regulation of neurotrophic function and neurotransmitter may be the mechanism for antidepressant‐like behavior. Together, these results demonstrate that PO is an antidepressant bioactive peptide accompanying the proliferation of hippocampal neural progenitor cells.