title: Glutamate and GABA imbalance promotes neuronal apoptosis in hippocampus after stress.
abstract: BACKGROUND
  People who experience traumatic events have an increased risk of post-traumatic stress disorder (PTSD). However, PTSD-related pathological changes in the hippocampus and prefrontal cortex remain poorly understood.
  
  
  METHODS
  We investigated the effect of a PTSD-like animal model induced by severe stress. The experimental rats received 20 inescapable electric foot shocks in an enclosed box for a total of 6 times in 3 days. The physiological state (body weight and plasma corticosterone concentrations), emotion, cognitive behavior, brain morphology, apoptosis, and balance of gamma-aminobutyric acid (GABA) and glutamate in the hippocampus and prefrontal cortex were observed. Cell damages were examined with histological staining (HE, Nissl, and silver impregnation), while apoptosis was analyzed with flow cytometry using an Annexin V and propidium iodide (PI) binding and terminal deoxynucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) method.
  
  
  RESULTS
  In comparison with the sham litter-mates, the stressed rats showed decreased body weight, inhibition of hypothalamic-pituitary-adrenal (HPA) axis activation, increase in freezing response to trauma reminder, hypoactivity and anxiety-like behaviors in elevated plus maze and open field test, poor learning in Morris water maze, and shortened latency in hot-plate test. There were significant damages in the hippocampus but not in the prefrontal cortex. Imbalance between glutamate and GABA was more evident in the hippocampus than in the prefrontal cortex.
  
  
  CONCLUSIONS
  These results suggest that neuronal apoptosis in the hippocampus after severe traumatic stress is related to the imbalance between glutamate and GABA. Such modifications may resemble the profound changes observed in PTSD patients.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Can
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China (mainland).
authors.forename: Ce
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000150:complications / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004644:Emotions; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000473:pathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003907:Dexamethasone