PMID- 25957094
OWN - NLM
STAT- MEDLINE
DCOM- 20160304
LR  - 20150606
IS  - 1532-2785 (Electronic)
IS  - 0143-4179 (Linking)
VI  - 51
DP  - 2015 Jun
TI  - Antidepressant-like effect of food-derived pyroglutamyl peptides in mice.
PG  - 25-9
LID - S0143-4179(15)00031-1 [pii]
LID - 10.1016/j.npep.2015.04.002 [doi]
AB  - The N-terminal glutamine residue, exposed by enzymatic cleavage of precursor 
      proteins, is known to be modified to a pyroglutamyl residue with a cyclic 
      structure in not only endogenous but also food-derived peptides. We investigated 
      the effects of wheat-derived pyroglutamyl peptides on emotional behaviors. 
      Pyroglutamyl leucine (pyroGlu-Leu, pEL) and pyroglutamyl glutaminyl leucine 
      (pyroGlu-Gln-Leu, pEQL) exhibited antidepressant-like activity in the tail 
      suspension and forced swim tests in mice. pEQL exhibited more potent 
      antidepressant-like activity than pEL after i.p. and i.c.v. administration. pEQL 
      exhibited antidepressant-like activity at a lower dose than Gln-Gln-Leu, 
      suggesting that pyroglutamyl peptide had more potent activity. To examine whether 
      pyroglutamyl peptides increased hippocampus neurogenesis, associated with the 
      effects of antidepressants, we measured 5-bromo-2'-deoxyuridine (BrdU) 
      incorporation. pEL and pEQL increased BrdU-positive cells in the dentate gyrus of 
      the hippocampus. Intriguingly, pEL did not increase hippocampal mRNA and protein 
      expression of brain-derived neurotrophic factor (BDNF), which is a factor 
      associated with both neuropoietic and antidepressive effects. Thus, pyroglutamyl 
      peptides may enhance hippocampal neurogenesis via a pathway independent of BDNF. 
      We also confirmed that pEL and pEQL were produced in the subtilisin digest of 
      major wheat proteins, glutenin and gliadin, after heat treatment. pEL and pEQL 
      are the first peptides derived from wheat proteins to be shown to exhibit an 
      antidepressant-like activity.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Yamamoto, Yukako
AU  - Yamamoto Y
AD  - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto 
      University, Gokasho Uji, Kyoto 611-0011, Japan.
FAU - Mizushige, Takafumi
AU  - Mizushige T
AD  - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto 
      University, Gokasho Uji, Kyoto 611-0011, Japan; Research Unit for Physiological 
      Chemistry, C-PIER, Kyoto University, Kyoto 606-8501, Japan.
FAU - Mori, Yukiha
AU  - Mori Y
AD  - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto 
      University, Gokasho Uji, Kyoto 611-0011, Japan.
FAU - Shimmura, Yuki
AU  - Shimmura Y
AD  - Health Care Research Center, R&D Division, Nisshin Pharma Inc., 5-3-1 Tsurugaoka, 
      Fujimino City, Saitama 356-8511, Japan.
FAU - Fukutomi, Ruuta
AU  - Fukutomi R
AD  - Health Care Research Center, R&D Division, Nisshin Pharma Inc., 5-3-1 Tsurugaoka, 
      Fujimino City, Saitama 356-8511, Japan.
FAU - Kanamoto, Ryuhei
AU  - Kanamoto R
AD  - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto 
      University, Gokasho Uji, Kyoto 611-0011, Japan.
FAU - Ohinata, Kousaku
AU  - Ohinata K
AD  - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto 
      University, Gokasho Uji, Kyoto 611-0011, Japan. Electronic address: 
      ohinata@kais.kyoto-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150422
PL  - Netherlands
TA  - Neuropeptides
JT  - Neuropeptides
JID - 8103156
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dipeptides)
RN  - 21282-11-1 (pyroglutamylleucine)
RN  - SZB83O1W42 (Pyrrolidonecarboxylic Acid)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology/therapeutic use
MH  - Behavior, Animal/*drug effects
MH  - Brain-Derived Neurotrophic Factor
MH  - Cell Proliferation/drug effects
MH  - Depression/drug therapy
MH  - Dipeptides/*pharmacology/therapeutic use
MH  - Hindlimb Suspension
MH  - Hippocampus/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Neurogenesis/*drug effects
MH  - Neurons/drug effects/metabolism
MH  - Pyrrolidonecarboxylic Acid/*analogs & derivatives/pharmacology/therapeutic use
MH  - Swimming
OTO - NOTNLM
OT  - Antidepressant-like effect
OT  - Emotional regulation
OT  - Gluten
OT  - Neurogenesis
OT  - Pyroglutamyl peptide
EDAT- 2015/05/10 06:00
MHDA- 2016/03/05 06:00
CRDT- 2015/05/10 06:00
PHST- 2014/12/17 00:00 [received]
PHST- 2015/03/19 00:00 [revised]
PHST- 2015/04/16 00:00 [accepted]
PHST- 2015/05/10 06:00 [entrez]
PHST- 2015/05/10 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
AID - S0143-4179(15)00031-1 [pii]
AID - 10.1016/j.npep.2015.04.002 [doi]
PST - ppublish
SO  - Neuropeptides. 2015 Jun;51:25-9. doi: 10.1016/j.npep.2015.04.002. Epub 2015 Apr 
      22.