title: Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models.
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.
authors.affiliation: Neuroscience, School of Life Sciences, University of Nottingham United Kingdom.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Pardon
authors.affiliation: Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham United Kingdom.|Medical Imaging Unit, School of Medicine, University of Nottingham United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Yanez Lopez
authors.affiliation: School of Computer Sciences, University of Nottingham United Kingdom.
authors.forename: Ding
authors.initials: D
authors.lastname: Yuchun
authors.affiliation: Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Marjańska
authors.affiliation: Medical Imaging Unit, School of Medicine, University of Nottingham United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Prior
authors.affiliation: School of Mathematics, University of Nottingham, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brignell
authors.affiliation: Neuroscience, School of Life Sciences, University of Nottingham United Kingdom.
authors.forename: Samira
authors.initials: S
authors.lastname: Parhizkar
authors.affiliation: Neuroscience, School of Life Sciences, University of Nottingham United Kingdom.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Agostini
authors.affiliation: School of Computer Sciences, University of Nottingham United Kingdom.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham United Kingdom.|Medical Imaging Unit, School of Medicine, University of Nottingham United Kingdom.
authors.forename: Dorothee P
authors.initials: DP
authors.lastname: Auer
authors.affiliation: Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham United Kingdom.|Medical Imaging Unit, School of Medicine, University of Nottingham United Kingdom.
authors.forename: Henryk M
authors.initials: HM
authors.lastname: Faas
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000276:immunology / Q000378:metabolism*
chemical_list: C491049:Aif1 protein, mouse; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; C528900:glial fibrillary astrocytic protein, mouse
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