PMID- 25386958
OWN - NLM
STAT- MEDLINE
DCOM- 20150717
LR  - 20190108
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 4
IP  - 11
DP  - 2014 Nov 11
TI  - Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal 
      pathway alterations and biomarker candidates.
PG  - e481
LID - 10.1038/tp.2014.119 [doi]
AB  - Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has fast-acting 
      antidepressant activities and is used for major depressive disorder (MDD) 
      patients who show treatment resistance towards drugs of the selective serotonin 
      reuptake inhibitor (SSRI) type. In order to better understand Ketamine's mode of 
      action, a prerequisite for improved drug development efforts, a detailed 
      understanding of the molecular events elicited by the drug is mandatory. In the 
      present study we have carried out a time-dependent hippocampal metabolite 
      profiling analysis of mice treated with Ketamine. After a single injection of 
      Ketamine, our metabolomics data indicate time-dependent metabolite level 
      alterations starting already after 2 h reflecting the fast antidepressant effect 
      of the drug. In silico pathway analyses revealed that several hippocampal 
      pathways including glycolysis/gluconeogenesis, pentose phosphate pathway and 
      citrate cycle are affected, apparent by changes not only in metabolite levels but 
      also connected metabolite level ratios. The results show that a single injection 
      of Ketamine has an impact on the major energy metabolism pathways. Furthermore, 
      seven of the identified metabolites qualify as biomarkers for the Ketamine drug 
      response.
FAU - Weckmann, K
AU  - Weckmann K
AD  - Department of Translational Research in Psychiatry, Max Planck Institute of 
      Psychiatry, Munich, Germany.
FAU - Labermaier, C
AU  - Labermaier C
AD  - Department of Translational Research in Psychiatry, Max Planck Institute of 
      Psychiatry, Munich, Germany.
FAU - Asara, J M
AU  - Asara JM
AD  - Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess 
      Medical Center, Harvard Medical School, Boston, MA, USA.
FAU - Muller, M B
AU  - Muller MB
AD  - Department of Translational Research in Psychiatry, Max Planck Institute of 
      Psychiatry, Munich, Germany.
FAU - Turck, C W
AU  - Turck CW
AD  - Department of Translational Research in Psychiatry, Max Planck Institute of 
      Psychiatry, Munich, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141111
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Biomarkers)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Biomarkers/metabolism
MH  - Excitatory Amino Acid Antagonists/administration & 
      dosage/*metabolism/pharmacology
MH  - Hippocampus/*drug effects/*metabolism
MH  - Ketamine/administration & dosage/*metabolism/pharmacology
MH  - Male
MH  - Metabolic Networks and Pathways/*drug effects
MH  - Metabolomics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
PMC - PMC4259990
EDAT- 2014/11/12 06:00
MHDA- 2015/07/18 06:00
PMCR- 2014/11/01
CRDT- 2014/11/12 06:00
PHST- 2014/07/01 00:00 [received]
PHST- 2014/09/12 00:00 [revised]
PHST- 2014/09/28 00:00 [accepted]
PHST- 2014/11/12 06:00 [entrez]
PHST- 2014/11/12 06:00 [pubmed]
PHST- 2015/07/18 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - tp2014119 [pii]
AID - 10.1038/tp.2014.119 [doi]
PST - epublish
SO  - Transl Psychiatry. 2014 Nov 11;4(11):e481. doi: 10.1038/tp.2014.119.