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-1 H-NMR (HRMAS-1 H-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.

UPLC/MS-Based Metabolomics Investigation of the Protective Effect of Hydrogen Gas Inhalation on Mice with Calcium Oxalate-Induced Renal Injury

“…When the mitochondria are dysfunctional, sebacic acid accumulates in the body and is unavailable for β-oxidation. 18,19) In our study, the sebacic acid concentration was higher in the CaOx group than the NO group and was at normal levels in the HO+CaOx group.…”

Metabolic Profiling of the Hippocampus of Rats Experiencing Nicotine-Withdrawal Symptoms

“…Rats with nicotine-withdrawal symptoms had reduced locomotor activity and increased anxiety, so it was determined that the Nic_12 group was experiencing nicotine-withdrawal symptoms. 14,15,18) In contrast, in the Nic_18 group, there was no significant change in crossing, rearing, and grooming time ( Figs. 2A-C).…”

“…The occurrences of grid line crossings, rearing, and grooming in the recorded video (5 min; minutes 1 to 6) were measured to assess the nicotinewithdrawal signs. 14,15,18) Sample Collection and Preparation Following the completion of the final OFT, rats were guillotined under diethyl ether anaesthesia. The brain was promptly removed, and the hippocampus was extracted by dividing the brain along the longitudinal fissure and rapidly freezing it in liquid nitrogen.…”

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

“…Alanine, aspartate, and glutamate pathways contribute to the development of depression, which was proved by metabolomic analysis of rats exposed to prenatal stress [38]. Assuming that alanine, glutamate, and glutamine are involved in energy exchange, in the citric acid cycle in particular, chronic exogenous stress could lead to energy exchange disruption in rats' brain tissue [39]. Metabolomic analysis of mononuclear cells from peripheral blood of rats exposed to chronic stress demonstrated defects of neurotransmitter metabolism, energy metabolism, and oxidative stress metabolism, such as lower concentration levels of aspartic and glutamic acids as compared to healthy rats [40].…”