title: Neuronal and astrocytic metabolism in a transgenic rat model of Alzheimer's disease.
abstract: Regional hypometabolism of glucose in the brain is a hallmark of Alzheimer's disease (AD). However, little is known about the specific alterations of neuronal and astrocytic metabolism involved in homeostasis of glutamate and GABA in AD. Here, we investigated the effects of amyloid β (Aβ) pathology on neuronal and astrocytic metabolism and glial-neuronal interactions in amino acid neurotransmitter homeostasis in the transgenic McGill-R-Thy1-APP rat model of AD compared with healthy controls at age 15 months. Rats were injected with [1-(13)C]glucose and [1,2-(13)C]acetate, and extracts of the hippocampal formation as well as several cortical regions were analyzed using (1)H- and (13)C nuclear magnetic resonance spectroscopy and high-performance liquid chromatography. Reduced tricarboxylic acid cycle turnover was evident for glutamatergic and GABAergic neurons in hippocampal formation and frontal cortex, and for astrocytes in frontal cortex. Pyruvate carboxylation, which is necessary for de novo synthesis of amino acids, was decreased and affected the level of glutamine in hippocampal formation and those of glutamate, glutamine, GABA, and aspartate in the retrosplenial/cingulate cortex. Metabolic alterations were also detected in the entorhinal cortex. Overall, perturbations in energy- and neurotransmitter homeostasis, mitochondrial astrocytic and neuronal metabolism, and aspects of the glutamate-glutamine cycle were found in McGill-R-Thy1-APP rats.
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Linn Hege
authors.initials: LH
authors.lastname: Nilsen
authors.affiliation: Centre for Neural Computation, Faculty of Medicine, Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Menno P
authors.initials: MP
authors.lastname: Witter
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ursula
authors.initials: U
authors.lastname: Sonnewald
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002952:Citric Acid Cycle; D004195:Disease Models, Animal; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D019289:Pyruvic Acid