Magnetic Resonance Spectroscopy of Metabolic Changes in the Brains of Mice Given 2-Deoxy-D-Glucose and Lipopolysaccharide

Abstract

Studies in ICR mice using proton magnetic resonance spectroscopy (1H MRS) addressed the metabolomic reaction of the hippocampus to deficiency of available energy induced by administration of 2-deoxy-Dglucose (2DG) and activation of the mechanisms of inflammation due to injection of bacterial lipopolysaccharide (LPS). Administration of 2DG increased the proportion of excitatory metabolites (glutamate and glutamine) and decreased the proportions of the inhibitory transmitter gamma-aminobutyric acid (GABA) and metabolites involved in neurogenesis (N-acetylaspartate (NAA) and choline compounds). Administration of LPS, conversely, increased the levels of GABA, NAA, and choline compounds. The differently directed effects of energy deficiency and proinflammatory stimuli explain the contradictory nature of 1H MRS results in patients with neurodegenerative pathologies, which in most cases are combined with mitochondrial dysfunction and inflammatory processes. The predominance of excitatory metabolites after administration of 2DG and inhibitory metabolites after administration of LPS are in good agreement with behavioral reactions seen in acute energy deficiencies, for example in hypoxia and illness behavior induced by proinflammatory factors.