title: Glutamine deficiency in the prefrontal cortex increases depressive-like behaviours in male mice.
abstract: 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.
  
  
  CONCLUSIONS
  Genetically modified animal models and diverse behavioural assessments would have been helpful to solidify our conclusions.
  
  
  CONCLUSIONS
  Neuronal Gln deficiency in the prefrontal cortex may cause depressive behaviours.
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
authors.forename: Younghyurk
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyeonwi
authors.initials: H
authors.lastname: Son
authors.forename: Gyeongwha
authors.initials: G
authors.lastname: Kim
authors.forename: Sujeong
authors.initials: S
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000209:etiology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000037:antagonists & inhibitors / Q000172:deficiency*; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017397:Prefrontal Cortex / Q000378:metabolism*
chemical_list: D000621:Aminoisobutyric Acids; D004791:Enzyme Inhibitors; D005973:Glutamine; D015074:2-Aminoadipic Acid; C017911:2-(methylamino)isobutyric acid; D018698:Glutamic Acid; D008715:Methionine; D005974:Glutamate-Ammonia Ligase; C013111:methionine sulfoxide