title: 1H NMR metabolomic signatures in five brain regions of the AβPPswe Tg2576 mouse model of Alzheimer's disease at four ages.
abstract: In the quest for biomarkers of onset and progression of Alzheimer's disease, a 1H NMR-based metabolomic study was performed on the simple single-transgenic Tg2576 mouse model. These mice develop a slow cognitive decline starting by 6 months and express amyloid plaques from 10 months of age. The metabolic profiles of extracts from five brain regions (frontal cortex, rhinal cortex, hippocampus, midbrain, and cerebellum) of Tg2576 male mice were compared to those of controls, at 1, 3, 6 and 11 months of age. The most obvious differences were due to brain regions. Age was also a discriminating parameter. Metabolic perturbations were already detected in the hippocampus and the rhinal cortex of transgenic mice as early as 1 month of age with decreased concentrations of glutamate (Glu) and N-acetylaspartate (NAA) compared to those in wild-type animals. Metabolic changes were more numerous in the hippocampus and the rhinal cortex of 3 month-old transgenic mice and involved Glu, NAA, myo-inositol, creatine, phosphocholine, and γ-aminobutyric acid (only in the hippocampus) whose concentrations decreased. A metabolic disruption characterized by an increase in the hippocampal concentrations of Glu, creatine, and taurine was detected in 6 month-old transgenic mice. At this time point, the chemical profile of the cerebellum was slightly affected. At 11 months, all the brain regions analyzed (except the frontal cortex) were metabolically altered, with mainly a marked increase in the formation of the neuroprotective metabolites creatine and taurine. Our findings demonstrate that metabolic modifications occur long before the onset of behavioral impairment.
authors.affiliation: Groupe de RMN Biomédicale, Laboratoire SPCMIB, Université de Toulouse, Toulouse cedex, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lalande
authors.affiliation: Centre de Recherches sur la Cognition Animale, Université de Toulouse, Toulouse cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Halley
authors.affiliation: Groupe de RMN Biomédicale, Laboratoire SPCMIB, Université de Toulouse, Toulouse cedex, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Balayssac
authors.affiliation: Groupe de RMN Biomédicale, Laboratoire SPCMIB, Université de Toulouse, Toulouse cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gilard
authors.affiliation: Institut de Mathématiques de Toulouse, Université de Toulouse, Toulouse cedex, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Déjean
authors.affiliation: Groupe de RMN Biomédicale, Laboratoire SPCMIB, Université de Toulouse, Toulouse cedex, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Martino
authors.affiliation: Centre de Recherches sur la Cognition Animale, Université de Toulouse, Toulouse cedex, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Francés
authors.affiliation: Centre de Recherches sur la Cognition Animale, Université de Toulouse, Toulouse cedex, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Lassalle
authors.affiliation: Groupe de RMN Biomédicale, Laboratoire SPCMIB, Université de Toulouse, Toulouse cedex, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Malet-Martino
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008636:Mesencephalon / Q000378:metabolism*; D055442:Metabolome / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D014020:Tissue Extracts / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D014020:Tissue Extracts; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
keywords: $^1$H NMR; Alzheimer's disease; AβPPswe Tg2576 mouse model; biomarkers; metabolomics