Increased astroglial activity and reduced neuronal function across brain in AβPP-PS1 mouse model of Alzheimer's...

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with progressive loss of cognitive function, personality, and behavior. The present study evaluates neuronal and astroglial metabolic activity, and neurotransmitter cycle fluxes in AβPP-PS1 mouse model of AD by using ¹H-[¹³C]-nuclear magnetic resonance (NMR) spectroscopy together with an infusion of either [1,6-¹³C₂]glucose or [2-¹³C]acetate. The levels of N-acetyl-aspartate (NAA) and glutamate were found to be decreased in the cerebral cortex and hippocampus in AβPP-PS1 mice, when compared with wild type controls. The cerebral metabolic rate of acetate oxidation was increased in the hippocampus and cerebral cortex of AβPP-PS1 mice suggesting enhanced astroglial activity in AD. AβPP-PS1 mice exhibit severe reduction in glutamatergic and gamma-amino butyric acid (GABA)ergic neuronal metabolic activity and neurotransmitter cycling fluxes in the hippocampus, cerebral cortex, and striatum as compared with controls. These data suggest that metabolic activity of excitatory and inhibitory neurons is compromised across brain in AβPP-PS1 mouse model of AD.