Document Detail


Glutamine deficiency in the prefrontal cortex increases depressive-like behaviours in male mice.
MedLine Citation:
PMID:  23031251     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The brain levels of glutamate (Glu) and glutamine (Gln) are partially regulated through the Glu-Gln cycle. Astrocytes play a role in regulating the Glu-Gln cycle, and loss of astrocytes has been associated with depressive disorders. We hypothesized that levels of Glu and Gln would be affected by astrocyte loss and dysregulation of the Glu-Gln cycle and that depressive-like behaviours would be closely related to the level of changes in Glu and Gln.
METHODS: We used liquid chromatography to measure Glu and Gln concentrations in the prefrontal cortex of male mice infused with L-α aminoadipic acid (L-AAA), a specific astrocyte toxin, in the prelimbic cortex. Methionine sulfoximine, a Gln synthetase inhibitor, and α-methyl-amino-isobutyric acid, a blocker of neuronal Gln transporters, were used to disturb the Glu-Gln cycle. We assessed the behavioural change by drug infusion using the forced swim test (FST) and sucrose preference test.
RESULTS: The Glu and Gln levels were decreased on the fifth day after L-AAA infusion, and the infused mice showed longer durations of immobility in the FST and lower sucrose preference, indicative of depressive-like behaviour. Mice in which Gln synthetase or Gln transport were inhibited also exhibited increased immobility in the FST. Direct infusion of L-Gln reversed the increased immobility induced by astrocyte ablation and Glu-Gln cycle impairments.
LIMITATIONS: Genetically modified animal models and diverse behavioural assessments would have been helpful to solidify our conclusions.
CONCLUSION: Neuronal Gln deficiency in the prefrontal cortex may cause depressive behaviours.
Authors:
Younghyurk Lee; Hyeonwi Son; Gyeongwha Kim; Sujeong Kim; Dong Hoon Lee; Gu Seob Roh; Sang Soo Kang; Gyeong Jae Cho; Wan Sung Choi; Hyun Joon Kim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of psychiatry & neuroscience : JPN     Volume:  38     ISSN:  1488-2434     ISO Abbreviation:  J Psychiatry Neurosci     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-12-09     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9107859     Medline TA:  J Psychiatry Neurosci     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  183-91     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
2-Aminoadipic Acid / pharmacology
Aminoisobutyric Acids / pharmacology
Analysis of Variance
Animals
Astrocytes / drug effects,  metabolism
Depressive Disorder / etiology*,  metabolism
Enzyme Inhibitors / pharmacology
Glutamate-Ammonia Ligase / antagonists & inhibitors
Glutamic Acid / metabolism
Glutamine / antagonists & inhibitors,  deficiency*
Male
Methionine / analogs & derivatives,  pharmacology
Mice
Mice, Inbred C57BL
Prefrontal Cortex / metabolism*
Chemical
Reg. No./Substance:
0/Aminoisobutyric Acids; 0/Enzyme Inhibitors; 0RH81L854J/Glutamine; 1K7B1OED4N/2-Aminoadipic Acid; 2566-34-9/2-(methylamino)isobutyric acid; 3KX376GY7L/Glutamic Acid; 454-41-1/methionine sulfoxide; AE28F7PNPL/Methionine; EC 6.3.1.2/Glutamate-Ammonia Ligase
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