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

Marie Christine Pardon, Maria Yanez Lopez, Ding Yuchun, Małgorzata Marjańska, Malcolm Prior, Christopher Brignell, Samira Parhizkar, Alessandra Agostini, Li Bai, Dorothee P. Auer, Henryk M. Faas

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20 Scopus citations

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. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker.

Original languageEnglish (US)
Article number19880
JournalScientific reports
Volume6
DOIs
StatePublished - Jan 27 2016

Bibliographical note

Funding Information:
This work was supported by the Medical Research Council (MRC) through an MRC “Confidence in Concept” award (CiC2014029), and UNICAS – a University of Nottingham initiative to fund interdisciplinary equipment-based research (UNICAS-A2B177). MM acknowledges the support from Biotechnology Research Center (BTRC) grant P41 EB015894 (NIBIB), and NCC P30 NS076408. We would like to thank Stacey Knapp and Michelle Hammett for technical support with histology.

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