PMID- 22384494
OWN - NLM
STAT- MEDLINE
DCOM- 20120320
LR  - 20221207
IS  - 0317-1671 (Print)
IS  - 0317-1671 (Linking)
VI  - 39
IP  - 1
DP  - 2012 Jan
TI  - Essential role of excessive tryptophan and its neurometabolites in fatigue.
PG  - 40-7
AB  - PURPOSE: Serotonin, a neurotransmitter synthesized from tryptophan, has been 
      proposed to play a key role in central fatigue. In this study, we examined 
      whether tryptophan itself and/or its two metabolites, kyneurenic acid (KYNA) and 
      quinolinic acid (QUIN), are involved in central fatigue. MATERIALS AND METHODS: 
      Experiments were conducted using Sprague-Dawley rats (SDR) and Nagase 
      analbuminemic rats (NAR). Central fatigue was assessed by treadmill running and a 
      Morris water maze test. Microdialysis was used to collect samples for measurement 
      of extracellular concentration of tryptophan, serotonin and 5-hydroxyindoleacetic 
      acid (5-HIAA) and to infuse test agents. To examine the kinetics of release, 
      synaptosomes in the striatum were prepared in vitro to measure intra- and 
      extrasynaptosomal concentration of tryptophan, serotonin and 5-HIAA. RESULTS: The 
      concentration of tryptophan secreted into the extracellular space of the striatum 
      was higher during fatigue only, and quickly returned to basal levels with 
      recovery from fatigue. Running time to exhaustion was reduced by activation of 
      tryptophan receptors. Time to exhaustion was shorter in NAR, which maintain a 
      higher extracellular level of striatum tryptophan than SDR. Impaired memory 
      performance in a water maze task after tryptophan treatment was attributable to 
      high levels of KYNA and QUIN in the hippocampus acting synergistically on 
      N-methyl-D-aspartic acid receptors. When branched-chain amino acids were 
      administered, tryptophan transport to the extracellular space of the striatum was 
      drastically inhibited. CONCLUSION: Our findings demonstrate that the increase in 
      fatigue which occurs because of excessively elevated brain tryptophan can be 
      further amplified by the use of synthetic KYNA and QUIN.
FAU - Yamamoto, Takanobu
AU  - Yamamoto T
AD  - University Laboratory of Neurophysiology, Department of Psychology, Tezukayama 
      University, Nara, Japan.
FAU - Azechi, Hirotsugu
AU  - Azechi H
FAU - Board, Mary
AU  - Board M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Can J Neurol Sci
JT  - The Canadian journal of neurological sciences. Le journal canadien des sciences 
      neurologiques
JID - 0415227
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - 8DUH1N11BX (Tryptophan)
RN  - EC 3.2.1.52 (Acetylglucosaminidase)
RN  - F6F0HK1URN (Quinolinic Acid)
RN  - H030S2S85J (Kynurenic Acid)
SB  - IM
MH  - Acetylglucosaminidase/deficiency/genetics
MH  - Amino Acids, Branched-Chain/therapeutic use
MH  - Analysis of Variance
MH  - Animals
MH  - Corpus Striatum/drug effects/metabolism/ultrastructure
MH  - Disease Models, Animal
MH  - Exercise Test/methods
MH  - Exploratory Behavior/drug effects/physiology
MH  - Fatigue/drug therapy/genetics/*metabolism/physiopathology
MH  - Female
MH  - Fluoxetine/pharmacology
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Kynurenic Acid/administration & dosage
MH  - Locomotion/drug effects/genetics
MH  - Maze Learning/drug effects/physiology
MH  - Microdialysis
MH  - Quinolinic Acid/administration & dosage
MH  - Rats
MH  - Rats, Mutant Strains
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
MH  - Stereotyped Behavior/drug effects/physiology
MH  - Synaptosomes/drug effects/metabolism
MH  - Time Factors
MH  - Tryptophan/*metabolism
EDAT- 2012/03/06 06:00
MHDA- 2012/03/21 06:00
CRDT- 2012/03/06 06:00
PHST- 2012/03/06 06:00 [entrez]
PHST- 2012/03/06 06:00 [pubmed]
PHST- 2012/03/21 06:00 [medline]
AID - 10.1017/s031716710001266x [doi]
PST - ppublish
SO  - Can J Neurol Sci. 2012 Jan;39(1):40-7. doi: 10.1017/s031716710001266x.