title: High-Resolution Magic-Angle Spinning-1H-NMR Spectroscopy-Based Metabolic Profiling of Hippocampal Tissue in Rats with Depression-Like Symptoms.
abstract: Depressive disorders cause large socioeconomic effects influencing not only the patients themselves but also their family and broader community as well. To better understand the physiologic factors underlying depression, in this study, we performed metabolomics analysis, an omics technique that comprehensively analyzes small molecule metabolites in biological samples. Specifically, we utilized high-resolution magic-angle spinning-1H-NMR (HRMAS-1H-NMR) spectroscopy to comprehensively analyze the changes in metabolites in the hippocampal tissue of rats exposed to chronic stress (CS) via multi-step principal component analysis (multi-step PCA). The rats subjected to CS exhibited obvious depression-like behaviors. High correlations were observed between the first principal component (PC1) score in the score plot obtained using multi-step PCA and measurements from depression-like behavioral testing (body weight, sucrose preference test, and open field test). Alanine, glutamate, glutamine, and aspartate levels in the hippocampal tissue were significantly lower, whereas N-acetylaspartate, myo-inositol, and creatine were significantly higher in the CS group compared to the control (non-CS) group. As alanine, glutamate, and glutamine are known to be involved in energy metabolism, especially in the tricarboxylic acid cycle, chronic exogenous stress may have induced abnormalities in energy metabolism in the brains of the rats. The results suggest that N-acetylaspartate and creatine levels may have increased in order to complement the loss of energy-producing activity resulting from the development of the depression-like disorder. Multi-step PCA therefore allowed an exploration of the degree of depression-like symptoms as represented by changes in intrinsic metabolites.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Hayato
authors.initials: H
authors.lastname: Akimoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Shinji
authors.initials: S
authors.lastname: Oshima
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.|Faculty of Pharmaceutical Sciences, Josai International University.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Ohara
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Akio
authors.initials: A
authors.lastname: Negishi
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST).
authors.forename: Hanako
authors.initials: H
authors.lastname: Hiroyama
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST).
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D025341:Principal Component Analysis; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D051381:Rats; D013315:Stress, Psychological
chemical_list: D000596:Amino Acids
keywords: N-acetylaspartate; brain tissue; depressive disorder; high-resolution magic-angle spinning-1H-NMR; metabolomics; multi-step principal component analysis