title: Decreased Glutamatergic Activity in the Frontal Cortex of Single Prolonged Stress Model: In vivo and Ex Vivo Proton MR Spectroscopy.
abstract: Single prolonged stress (SPS) is one of the preclinical models of posttraumatic stress disorder (PTSD) in humans. Not every traumatized person develops PTSD and the onset of the disease varies from months to many years after exposure to life-threatening events. The pathogenetic neurometabolites in PTSD have not been investigated to date, and could provide a means for therapeutic interventions. Therefore the present study aimed to evaluate neurochemical changes in the frontal cortex in the SPS model during time-dependent sensitization using in vivo and ex vivo proton magnetic spectroscopy (1H-MRS). Twenty-one male Sprague-Dawley rats (200-220 g) were randomly assigned into two groups (Control, n = 10; SPS, n = 11). SPS consists of three consecutive stressors (restraint, forced swimming, and ether exposure) followed by 7 days without disturbance. In vivo1H-MRS scans were conducted at baseline, immediately after SPS, and 3 and 7 days after SPS to quantify time-dependent alterations in the frontal cortex. On day 7, all animals were sacrificed and ex vivo1H-MRS was performed. After SPS exposure, the SPS group showed signs of excitatory activities (glutamate) and cellular membrane turnover (choline and total choline) for 7 days. After the time-sensitization period, the SPS group showed lower glutamate and creatine levels and higher choline and lactate levels than the control group. These results indicate that SPS induces sustained adaptation of glutamatergic neuronal activity in the frontal cortex. Therefore, we conclude that SPS-induced stress reduces glutamatergic metabolism in the frontal cortex.
authors.affiliation: Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Song-I
authors.initials: SI
authors.lastname: Lim
authors.affiliation: Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Kyu-Ho
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Chi-Hyeon
authors.initials: CH
authors.lastname: Yoo
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Woo
authors.affiliation: Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. bychoe@catholic.ac.kr.|Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. bychoe@catholic.ac.kr.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Choe
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid
keywords: Frontal cortex; Glutamate; High resolution magic angle spinning (HR-MAS); Posttraumatic stress disorder (PTSD); Proton magnetic resonance spectroscopy (¹H MRS); Single prolonged stress (SPS)