Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models

Scientific Reports
Marie-Christine PardonHenryk M Faas

Abstract

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimer's disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimer's disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lip...Continue Reading

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Citations

Oct 20, 2018·Journal of Neurochemistry·Aisling ChaneyHerve Boutin
Aug 14, 2018·Journal of Neuroscience Methods·Meghann C RyanStephen McGuire
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wanqi HuXiaobo Qu

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Methods Mentioned

BETA
NMR
transgenic

Software Mentioned

ParaVision
InVivoStat
Matlab
ARRIVE
LCModel

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