White matter imaging, microstructure, and negative affetcs: thanslational study in humans and mice
The present project, capitalizes on novel cutting edge technology and proposes to build a highly synergistic effort, and an unprecedented translational collaboration between clinical and basic scientists and experts in the myelin field from three countries, to study the significance of white matter alterations in initial depression and related symptoms. We propose to follow up an existing cohort of community adolescents, recruit young adult MDD patients, exploit the ressources of a unique post-mortem human brain bank, and introduce relevant translational animal models, with the objectives to: o Identify brain morphometry and WM microstructure (DTI) changes that correlate with similar affective dimensions encompassing anxiety and depression symptoms, in both in humans and animals, as common imaging biomarkers with translational value. o Determine specific morphological myelin structure changes (myelin sheaths diameter, axon number, myelinated fibers number, myelin genes?) that underlie imaging findings in mice. o Characterize the cellular and molecular white matter microenvironments in the same white matter bundles of post-mortem brain samples from patients with Major Depressive Disorder (MDD). Get insight into the potential pathophysiological mechanisms that link altered white matter integrity with depression and related symptoms, focusing on local inflammatory processes and relevant signalling pathways, in humans and mice. Magnetic-resonance imaging (MR) and diffusion tensor imaging (DTI) in young adult participants is paralleled by the use of high-resolution ex vivo imaging in animals. DTI in animals will be combined with state-of-the art electron microscopy, molecular and biochemical techniques. The molecular determinations in animals will be paralleled by investigations with analogous markers in human brain tissues, in the same bundles connecting the negative affect network This comprehensive approach has the potential to provide new pathophysiological hypotheses on white matter and negative affects but also clinical biomarkers to inform early intervention and diagnosis strategies.
affective disorders, Imaging techniques, Molecular and (epi)genetic and "omics" approaches, Behavioural methodologies, brain structure, connectivity
2013 - 2016
Jea-Luc Martinot (Coordinator)