PMID- 25533534
OWN - NLM
STAT- MEDLINE
DCOM- 20160329
LR  - 20220316
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 40
IP  - 6
DP  - 2015 May
TI  - The sleep-promoting and hypothermic effects of glycine are mediated by NMDA 
      receptors in the suprachiasmatic nucleus.
PG  - 1405-16
LID - 10.1038/npp.2014.326 [doi]
AB  - The use of glycine as a therapeutic option for improving sleep quality is a novel 
      and safe approach. However, despite clinical evidence of its efficacy, the 
      details of its mechanism remain poorly understood. In this study, we investigated 
      the site of action and sleep-promoting mechanisms of glycine in rats. In acute 
      sleep disturbance, oral administration of glycine-induced non-rapid eye movement 
      (REM) sleep and shortened NREM sleep latency with a simultaneous decrease in core 
      temperature. Oral and intracerebroventricular injection of glycine elevated 
      cutaneous blood flow (CBF) at the plantar surface in a dose-dependent manner, 
      resulting in heat loss. Pretreatment with N-methyl-D-aspartate (NMDA) receptor 
      antagonists AP5 and CGP78608 but not the glycine receptor antagonist strychnine 
      inhibited the CBF increase caused by glycine injection into the brain. Induction 
      of c-Fos expression was observed in the hypothalamic nuclei, including the medial 
      preoptic area (MPO) and the suprachiasmatic nucleus (SCN) shell after glycine 
      administration. Bilateral microinjection of glycine into the SCN elevated CBF in 
      a dose-dependent manner, whereas no effect was observed when glycine was injected 
      into the MPO and dorsal subparaventricular zone. In addition, microinjection of 
      D-serine into the SCN also increased CBF, whereas these effects were blocked in 
      the presence of L-701324. SCN ablation completely abolished the sleep-promoting 
      and hypothermic effects of glycine. These data suggest that exogenous glycine 
      promotes sleep via peripheral vasodilatation through the activation of NMDA 
      receptors in the SCN shell.
FAU - Kawai, Nobuhiro
AU  - Kawai N
AD  - Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
FAU - Sakai, Noriaki
AU  - Sakai N
AD  - Sleep and Circadian Neurobiology laboratory, Stanford University School of 
      Medicine, Stanford, CA, USA.
FAU - Okuro, Masashi
AU  - Okuro M
AD  - 1] Sleep and Circadian Neurobiology laboratory, Stanford University School of 
      Medicine, Stanford, CA, USA [2] Department of Geriatric Medicine, Kanazawa 
      Medical University, Kanazawa, Japan.
FAU - Karakawa, Sachie
AU  - Karakawa S
AD  - Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
FAU - Tsuneyoshi, Yosuke
AU  - Tsuneyoshi Y
AD  - Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
FAU - Kawasaki, Noriko
AU  - Kawasaki N
AD  - Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
FAU - Takeda, Tomoko
AU  - Takeda T
AD  - Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
FAU - Bannai, Makoto
AU  - Bannai M
AD  - Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
FAU - Nishino, Seiji
AU  - Nishino S
AD  - Sleep and Circadian Neurobiology laboratory, Stanford University School of 
      Medicine, Stanford, CA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141223
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Autonomic Agents)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Receptors, Glycine)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Autonomic Agents/*pharmacology
MH  - Body Temperature/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Glycine/*pharmacology
MH  - Hypnotics and Sedatives/*pharmacology
MH  - Male
MH  - Preoptic Area/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Random Allocation
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Receptors, Glycine/agonists/antagonists & inhibitors/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism
MH  - Regional Blood Flow/drug effects/physiology
MH  - Skin/blood supply/drug effects
MH  - Sleep/drug effects/physiology
MH  - Suprachiasmatic Nucleus/*drug effects/*metabolism
PMC - PMC4397399
EDAT- 2014/12/24 06:00
MHDA- 2016/03/30 06:00
PMCR- 2016/05/01
CRDT- 2014/12/24 06:00
PHST- 2014/05/15 00:00 [received]
PHST- 2014/11/17 00:00 [revised]
PHST- 2014/12/01 00:00 [accepted]
PHST- 2014/12/24 06:00 [entrez]
PHST- 2014/12/24 06:00 [pubmed]
PHST- 2016/03/30 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - npp2014326 [pii]
AID - 10.1038/npp.2014.326 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2015 May;40(6):1405-16. doi: 10.1038/npp.2014.326. Epub 
      2014 Dec 23.