Neurochemical Changes Associated with Stress-Induced Sleep Disturbance in Rats: In Vivo and In Vitro Measurements

PLoS One. 2016 Apr 14;11(4):e0153346. doi: 10.1371/journal.pone.0153346. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Dopamine / analysis
  • Glutamine / analysis
  • Magnetic Resonance Imaging
  • Male
  • Radiography
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / analysis
  • Sleep Wake Disorders / diagnostic imaging
  • Sleep Wake Disorders / etiology
  • Sleep Wake Disorders / metabolism*
  • Stress, Psychological*
  • Tandem Mass Spectrometry*
  • gamma-Aminobutyric Acid / analysis

Substances

  • Glutamine
  • Serotonin
  • gamma-Aminobutyric Acid
  • Dopamine

Associated data

  • figshare/10.6084/M9.FIGSHARE.3156595
  • figshare/10.6084/M9.FIGSHARE.3156598
  • figshare/10.6084/M9.FIGSHARE.3156601
  • figshare/10.6084/M9.FIGSHARE.3156604
  • figshare/10.6084/M9.FIGSHARE.3156607

Grants and funding

This study was supported by grants of Basic Science Research Program through the National Research Foundation of Korea funded [NRF (www.nrf.re.kr): NRF-2015R1C1A1A02036526], by the Ministry of Science, Korea (DCW), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute [KHIDI (www.khidi.or.kr): HI14C1090], funded by the Ministry of Health & Welfare, Republic of Korea (DCW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.