PMID- 29161812
OWN - NLM
STAT- MEDLINE
DCOM- 20181112
LR  - 20181112
IS  - 1520-5118 (Electronic)
IS  - 0021-8561 (Linking)
VI  - 65
IP  - 49
DP  - 2017 Dec 13
TI  - Acute Amino Acid d-Serine Administration, Similar to Ketamine, Produces 
      Antidepressant-like Effects through Identical Mechanisms.
PG  - 10792-10803
LID - 10.1021/acs.jafc.7b04217 [doi]
AB  - d-Serine is an amino acid and can work as an agonist at the glycine sites of 
      N-methyl-d-aspartate receptor (NMDAR). Interestingly, both types of glutamatergic 
      modulators, NMDAR enhancers and blockers, can improve depression through common 
      targets, namely alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid 
      receptors (AMPARs) and mammalian target of rapamycin (mTOR). To elucidate the 
      cellular signaling pathway underlying this counterintuitive observation, we 
      activated NMDARs in rats by using d-serine. Saline, ketamine (NMDAR antagonist), 
      and desipramine (tricyclic antidepressant) were used as controls. The 
      antidepressant-like effects of all agents were evaluated using the forced swim 
      test. The activation of the AMPAR-mTOR signaling pathway, release of 
      brain-derived neurotrophic factor (BDNF), and alteration of AMPAR and NMDAR 
      trafficking in the hippocampus of rats were examined. A single high dose of 
      d-serine exerted an antidepressant-like effect that was mediated by rapid 
      AMPAR-induced mTOR signaling pathway and increased BDNF proteins, identical to 
      that of ketamine. Furthermore, in addition to the increased protein kinase A 
      phosphorylation of the AMPAR subunit GluR1 (an indicator of AMPAR insertion in 
      neurons), treatment with individual optimal doses of d-serine and ketamine also 
      increased adaptin beta2-NMDAR association (an indicator of the intracellular 
      endocytic machinery and subsequent internalization of NMDARs). Desipramine did 
      not influence these processes. Our study is the first to demonstrate an 
      association between d-serine and ketamine; following adaptative regulation of 
      AMPAR and NMDAR may lead to common changes of them. These findings provide novel 
      targets for safer antidepressant agents with mechanisms similar to those of 
      ketamine.
FAU - Wei, I-Hua
AU  - Wei IH
FAU - Chen, Kuang-Ti
AU  - Chen KT
FAU - Tsai, Mang-Hung
AU  - Tsai MH
FAU - Wu, Ching-Hsiang
AU  - Wu CH
AD  - Department of Anatomy, College of Medicine, Taipei Medical University , 110 
      Taipei, Taiwan.
FAU - Lane, Hsien-Yuan
AU  - Lane HY
AD  - Brain Disease Research Center & Department of Psychiatry, China Medical 
      University Hospital , 404 Taichung, Taiwan.
FAU - Huang, Chih-Chia
AU  - Huang CC
AUID- ORCID: 0000-0001-8703-1878
AD  - Brain Disease Research Center & Department of Psychiatry, China Medical 
      University Hospital , 404 Taichung, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20171204
PL  - United States
TA  - J Agric Food Chem
JT  - Journal of agricultural and food chemistry
JID - 0374755
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate 
      receptor, human)
RN  - 452VLY9402 (Serine)
RN  - 690G0D6V8H (Ketamine)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/administration & dosage/*chemistry/*pharmacology
MH  - Apoptosis
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Depression/drug therapy
MH  - Hippocampus/drug effects
MH  - Humans
MH  - Ketamine/administration & dosage/chemistry/*pharmacology
MH  - Kidney/metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Neurons/drug effects/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Glutamate/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Serine/administration & dosage/*chemistry/*pharmacology
MH  - Swimming
OTO - NOTNLM
OT  - AMPA
OT  - NMDA
OT  - amino acid
OT  - d-serine
OT  - depression
OT  - ketamine
OT  - trafficking
EDAT- 2017/11/23 06:00
MHDA- 2018/11/13 06:00
CRDT- 2017/11/23 06:00
PHST- 2017/11/23 06:00 [pubmed]
PHST- 2018/11/13 06:00 [medline]
PHST- 2017/11/23 06:00 [entrez]
AID - 10.1021/acs.jafc.7b04217 [doi]
PST - ppublish
SO  - J Agric Food Chem. 2017 Dec 13;65(49):10792-10803. doi: 10.1021/acs.jafc.7b04217. 
      Epub 2017 Dec 4.