title: Neurochemical Changes Associated with Stress-Induced Sleep Disturbance in Rats: In Vivo and In Vitro Measurements.
abstract: The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue. In the right dorsal hippocampal region, the gamma-aminobutyric-acid (GABA) and glutamine (Gln) concentrations were significantly higher in the sleep-perturbed rats than in the sham controls. The ratios of Gln/Glu (glutamate), Gln/tCr (total-creatine), and GABA/Glu were also significantly higher in the sleep-perturbed group, while serotonin concentrations were significantly lower in the sleep-perturbed rats. Pearson correlation results among individual rat data indicate that concentrations of dopamine (DA) and serotonin (5-HT) were significantly higher in SSP rats. A larger correlation coefficient was also observed for the SSP rats. Analysis of the correlation between the in vivo and in vitro signals indicated that the concentrations of Gln, 5-HT, and DA exhibited a significant negative correlation in the SSP rat data but not in that of control rats. The authors propose that the altered and correlated GABA, Gln, 5-HT, and DA concentrations/ratios could be considered key markers of neurological function in animal models of stress-induced sleep perturbation.
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|MR Core Laboratory, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Do-Wan
authors.initials: DW
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Seockhoon
authors.initials: S
authors.lastname: Chung
authors.affiliation: Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: MR Core Laboratory, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Chul-Woong
authors.initials: CW
authors.lastname: Woo
authors.affiliation: MR Core Laboratory, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Sang-Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jeong-Kon
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jin Seong
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Choong Gon
authors.initials: CG
authors.lastname: Choi
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Shim
authors.affiliation: MR Core Laboratory, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Yoonseok
authors.initials: Y
authors.lastname: Choi
authors.affiliation: MR Core Laboratory, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Woo
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D005973:Glutamine / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis; D012893:Sleep Wake Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D013315:Stress, Psychological; D053719:Tandem Mass Spectrometry; D005680:gamma-Aminobutyric Acid / Q000032:analysis
chemical_list: D005973:Glutamine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine