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Direct mapping of Krebs cycle activity in the male and female brain at subcellular resolution using soft x-ray fluorescence

DOI: 10.1017/S1431927618014010 DOI Help

Authors: C. Poitry-yamate (Ecole Polytechnique Federale de Lausanne) , M. Abyaneh (Diamond Light Source) , T. Araki (Diamond Light Source) , M. Lepore (Ecole Polytechnique Federale de Lausanne) , B. Kaulich (Diamond Light Source) , R. Gruetter (Ecole Polytechnique Federale de Lausanne)
Co-authored by industrial partner: No

Type: Conference Paper
Conference: Microscopy & Microanalysis 2018
Peer Reviewed: No

State: Published (Approved)
Published: August 2018

Abstract: Fluoroacetate (FA), a plant toxin and intermediate product of anticancer agents, integrates itself into the Krebs cycle by substituting for acetate to form fluorocitrate. The function of this key metabolic cycle in glucose metabolism is disabled when fluorocitrate binds to aconitase. FA purportedly disrupts the Krebs cycle selectively in non-neuronal cells, i.e. glia/astrocytes, making it the substance of choice by which to assess the importance of glia for brain function in the living animal. However, since acetate, considered a marker of glial oxidative metabolism, can also be transported into neurons begs the question whether FA uptake, metabolism, and compartmentation is glial-selective in vivo, and whether this can be experimentally imaged; as important, is whether the first phase of brain glucose metabolism, i.e. glycolysis is affected. Dynamic cerebral 18FDG (glucose) PET in the living rat, and low energy x-ray fluorescence chemical imaging of such brains, albeit freeze substitution-fixed and epon infiltrated, were implemented to address these questions, and enabled testing our working hypothesis that sexual dimorphism of brain structure and function extends to metabolism as well.

Subject Areas: Biology and Bio-materials

Instruments: I08-Scanning X-ray Microscopy beamline (SXM)