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Laboratory | Cell and molecular imaging

Molecular Imaging and Delivery of Active Substances

SIGMA project


Adaptive and maladaptive response to stress: a longitudinal brain imaging characterization with molecular correlates​

Published on 28 November 2017

3 years duration, ANR grant AAP BLANC INTERNATIONAL II 2012, coordinator T. Jay (CPN)
Collaboration with others researchers working at NeuroSpin: Michel Bottlaender (UNIACT), Cyril Poupon (UNIRS), Fawzi Boumezbeur (UNIRS)

Affective disorders result from a gene‐environment interaction with stress as a risk factor that may precipitate their emergence. In some cases acute or repeated stress leads to affective disorders, but most people are resilient to such effects. The ability to adapt during stress has a significant impact on the functional outcome and long‐term health of each individual. Whereas physiological and behavioral effects of stress have been already reported in human and animal studies, there are only a few researches focusing on adaptive and maladaptive response to stress. Recent studies combining behavioral, molecular and electrophysiological techniques and the use of animal models reveal that stress may induce memory impairment, neuroplastic changes in specific neural circuits and at the cellular level drastic effects, including cell death. The study of stress‐induced events requires diachronic approaches; thus, the use of longitudinal in vivo MRI combined to ex vivo characterization (molecular and imaging) becomes critical for the analysis of the neurobiology of stress.​

In this project, we plan to investigate changes in the function and structure of the brain that are associated to the normal and pathological response to repeated stress. To fulfill this goal, multimodal MRI data will be acquired both in vivo and ex vivo to compare potential effects of acute and repeated stress in two rat strains exhibiting different sensitivities to stress. Concomitantly, molecular markers of stress will be detected in several brain regions of these two rat strains, in order to identify potential correlations between stress-associated changes highlighted on anatomical and functional MRI data (cerebral structure, function, white matter microstructure and connectivity) and on quantitative measurements of specific molecular markers (markers of functional and structural brain activity, inflammatory signaling). The chosen longitudinal approach will allow assessing significant brain changes at different times of exposure to stress and between high and low stress‐sensitive rat strains: 1) comparison between baselines will provide biomarkers of vulnerability to stress; 2) comparison before and after exposure to acute stress will provide biomarkers of acute stress effects and 3) comparison before and after exposure to repeated stress will provide biomarkers of habituation. Investigating the neural circuits and molecular pathways of resilience will provide a tool for mechanistic understanding of stress effects on neural systems. It will also potentiate MRI for in vivo monitoring of response to stress in preclinical and clinical research. Understanding the mechanisms of resilience to stress will offer a crucial new dimension for the development of fundamentally novel treatments to the protection of stress effects.


 
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