title: In vivo 1H MRS study in microlitre voxels in the hippocampus of a mouse model of Down syndrome at 11.7 T.
abstract: In this article, we report in vivo (1)H MRS performed in 1.8-μL voxels in a mouse model of Down syndrome (DS). To characterise the excitation-inhibition imbalance observed in DS, metabolite concentrations in the hippocampi of adult Ts65Dn mice, which recapitulate features of DS, were compared with those of their euploid littermates at a voxel 42-fold smaller than in a previously published study. Quantification of the metabolites was performed using a linear combination model. We detected 16 metabolites in the right and left hippocampi. Principal component analysis revealed that the absolute concentrations of the 16 detected metabolites could differentiate between Ts65Dn and euploid hippocampi. Although measurements in the left and right hippocampi were highly correlated, the concentration of individual metabolites was sometimes significantly different in the left and right structures. Thus, bilateral values from Ts65Dn and euploid mice were further compared with Hotelling's test. The level of glutamine was found to be significantly lower, whereas myo-inositol was significantly higher, in the hippocampi of Ts65Dn relative to euploid mice. However, γ-aminobutyric acid (GABA) and glutamate levels remained similar between the groups. Thus, the excitation-inhibition imbalance described in DS does not appear to be related to a radical change in the levels of either GABA or glutamate in the hippocampus. In conclusion, microliter MRS appears to be a valuable tool to detect changes associated with DS, which may be useful in investigating whether differences can be rescued after pharmacological treatments or supplementation with glutamine.
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, 75013, Paris, France; Centre de NeuroImagerie de Recherche, ICM, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Mathieu D
authors.initials: MD
authors.lastname: Santin
authors.forename: Romain
authors.initials: R
authors.lastname: Valabrègue
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rivals
authors.forename: Romain
authors.initials: R
authors.lastname: Pénager
authors.forename: Raphaël
authors.initials: R
authors.lastname: Paquin
authors.forename: Luce
authors.initials: L
authors.lastname: Dauphinot
authors.forename: Christelle
authors.initials: C
authors.lastname: Albac
authors.forename: Benoit
authors.initials: B
authors.lastname: Delatour
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Potier
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D004195:Disease Models, Animal; D004292:Dominance, Cerebral; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D059906:Neuroimaging / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Down syndrome; MRS; hippocampus; inhibition; metabolite