Multiparametric magnetic resonance and phenotyping studies of a depression rat model: Identifying in vivo and ex vivo biomarkers

Resumen del trabajo presentado al 32nd Annual Scientific Meeting of European Society for Magnetic Resonance In Medicine and Biology, celebrado en Edinburgo (UK) del 1 al 3 de octubre de 2015.[Purpose/Introduction]: Depression is a mental disorder that alters individual’s disposition and involves depressed mood and feelings of sadness, worthlessness and culpability. It is a severe condition whose prevalence has increased, with the social and health problem that this entails. Currently, there is not any clinical approach in order to validate either the progress of the illness or the outcome of therapies, and it would be really helpful to find surrogate markers of this pathology evolution. On the other hand, magnetic resonance allows the in vivo and ex vivo evaluation of the healthy and diseased brain in a non-invasive way. We aimed to employ MR to identifying biomarkers in an animal model of depression. [Subjects and Methods]: Experiments used adult male Wistar rats submitted to a Chronic Mild Stress protocol (n=12) and healthy animal as control (n=12). MRI experiments were performed on a 7.0-T system and consisted in: i) T2W-images, ii) magnetization transfer imaging, iii) diffusion-weighted imaging. Brain regions (hippocampus, hypothalamus, somatosensory cortex and motor cortex) were analyzed in the computed parametric maps: MTR, ADC and FA. Animals were also studied in a phenotyping platform for an automated metabolic, behavioral, and physiological monitoring. Indirect gas calorimetry, food/liquid intake and locomotor activity data were analyzed. Rats were sacrificed and brain excised to acquire 1H HR-MAS spectra of brain regions in an 11.7-T vertical magnet. [Results]: Volumetric measurements showed, in pathological animals compared to controls, a slight reduction of hippocampal related to brain volume (10.9% vs 11.4%). MTR values increased in depressed animals whereas ADC's were reduced. FA data presented a different behavior depending on the region, increasing in hippocampus and hypothalamus, but decreasing in cortex. Metabolic and motor activity studies offered differences in darkness measurements yielding lower values in diseased animals. Metabolomic analysis from ex vivo spectra showed a lower concentration of some metabolites in pathological animals: neurotransmitters (glutamine and glutamate), neuronal markers (N-acetyl-aspartate), and osmolytes (myoinositol and taurine). [Discussion/Conclusion]: The in vivo studies have identified differences in structural, functional and activity parameters of animals submitted to CMS protocol, probably linked to inflammatory events taken place in the brain. Results from ex vivo analysis have also signaled changes in cerebral metabolites. These quantitative parameters could be used like biomarkers of the disease in diagnosis and therapies validation.Peer Reviewe