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Joao Duarte

Principal investigator

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Alterations of Brain Energy Metabolism in Type 2 Diabetic Goto-Kakizaki Rats Measured In Vivo by (13)C Magnetic Resonance Spectroscopy

Author

  • Freya-Merret Girault
  • Sarah Sonnay
  • Rolf Gruetter
  • João M N Duarte

Summary, in English

Type 2 diabetes (T2D) is associated with deterioration of brain structure and function. Here, we tested the hypothesis that T2D induces a reorganization of the brain metabolic networks that support brain function. For that, alterations of neuronal and glial energy metabolism were investigated in a T2D model, the Goto-Kakizaki (GK) rat. (13)C magnetic resonance spectroscopy in vivo at 14.1 T was used to detect (13)C labeling incorporation into carbons of glutamate, glutamine, and aspartate in the brain of GK (n = 7) and Wistar (n = 13) rats during intravenous [1,6-(13)C]glucose administration. Labeling of brain glucose and amino acids over time was analyzed with a two-compartment mathematical model of brain energy metabolism to determine the rates of metabolic pathways in neurons and glia. Compared to controls, GK rats displayed lower rates of brain glutamine synthesis (- 32%, P < 0.001) and glutamate-glutamine cycle (- 40%, P < 0.001), and mitochondrial tricarboxylic acid (TCA) cycle rate in neurons (- 7%, P = 0.036). In contrast, the TCA cycle rate of astrocytes was larger in GK rats than controls (+ 21%, P = 0.042). We conclude that T2D alters brain energy metabolism and impairs the glutamate-glutamine cycle between neurons and astrocytes, in line with diabetes-induced neurodegeneration and astrogliosis underlying brain dysfunction.

Publishing year

2019

Language

English

Pages

268-278

Publication/Series

Neurotoxicity Research

Volume

36

Issue

2

Document type

Journal article

Publisher

Springer

Keywords

  • Journal Article

Status

Published

ISBN/ISSN/Other

  • ISSN: 1029-8428