Neuro-metabolite profiles of rodent models of psychiatric dysfunctions characterised by MR spectroscopy.

Autor: Sekar S; Singapore Bioimaging Consortium, Agency for Science, Technology & Research, Singapore., Grandjean J; Singapore Bioimaging Consortium, Agency for Science, Technology & Research, Singapore., Garnell JF; Singapore Bioimaging Consortium, Agency for Science, Technology & Research, Singapore., Willems R; Neuroscience Discovery, Janssen Research and Development, Beerse, Belgium., Duytschaever H; Neuroscience Discovery, Janssen Research and Development, Beerse, Belgium., Seramani S; Singapore Bioimaging Consortium, Agency for Science, Technology & Research, Singapore., Su H; Institute for Infocomm Research, Agency for Science, Technology & Research, Singapore., Ver Donck L; Neuroscience Discovery, Janssen Research and Development, Beerse, Belgium., Bhakoo KK; Singapore Bioimaging Consortium, Agency for Science, Technology & Research, Singapore. Electronic address: kishore_bhakoo@sbic.a-star.edu.sg.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2019 Mar 01; Vol. 146, pp. 109-116. Date of Electronic Publication: 2018 Nov 23.
DOI: 10.1016/j.neuropharm.2018.11.021
Abstrakt: Neuroimaging endophenotypes in animal models provide an objective and translationally-relevant alternative to cognitive/behavioral traits in human psychopathologies. Metabolic alterations, such as those involved in the glutamate-cycle, have been proposed to play a preponderant role in both depression and schizophrenia. Chronic Mild Unpredictable Stress (CMUS) and sub-chronic administration of NMDA receptor antagonist generate animal models of depression and schizophrenia, respectively. The models are based on etiologically-relevant factors related to the induction and support of these psychopathologies. To test metabolic alterations within the glutamate-cycle and in other major neurochemicals, single-voxel Magnetic Resonance Spectroscopy was recorded within the hippocampus in both rat models and control animals. Surprisingly, altered glutamate-related metabolites were observed in the CMUS model, but not NMDA-based model, as indicated by decreased glutamine and increased GABA levels. However, both models presented elevated total visible choline and inositol levels relative to controls. These results indicate the presence cell membrane metabolic alterations and inflammatory processes shared in both models, comparable to evidence presented in schizophrenia and depression and other comparable animal models. These translationally-relevant biomarkers may thus form the basis for drug-development targets in both psychopathologies.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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