Neuropsychiatric disorders are a heterogeneous group of mental pathologies that demand prolonged and treatments that are frequently ineffective. Elucidating the cellular and molecular mechanisms under

Description du projet

Ouvrir la boîte noire de l’espace extracellulaire

Le système nerveux central est composé de milliards de cellules. Les membranes cellulaires créent deux compartiments généralement distincts, l’espace intracellulaire et extracellulaire. L’espace extracellulaire occupe environ un cinquième du volume cérébral et il remplit même les plus petits interstices entre les cellules. Alors que les cellules, leurs constituants et même le mouvement des substances à travers les membranes ont été largement étudiés, le micro-environnement 3D complexe entourant les cellules reste un terrain assez méconnu. NanoPSYCH utilise de nouveaux outils de nanotechnologie et de biotechnologie pour examiner la structure de l’espace extracellulaire et, en particulier, la manière dont il affecte l’accumulation d’auto-anticorps. L’auto-immunité a récemment été liée aux troubles neuropsychiatriques, et NanoPSYCH espère faire la lumière sur les mécanismes neurobiologiques de ces affections.

Objectif

Neuropsychiatric disorders are a heterogeneous group of mental pathologies that demand prolonged and treatments that are frequently ineffective. Elucidating the cellular and molecular mechanisms underlying these diseases is paramount for a precise classification of subgroups of patient and application of appropriate therapeutic strategies. The role of the immune system in the pathophysiology of neuropsychiatric disorders has been the subject of debate for many decades. However, recent recognition of antibody-mediated central nervous system (CNS) disorders has fueled the search for a subgroup of patients with an antibody-mediated psychiatric illness. CNS autoantibodies have demonstrated to be pathogenic by disrupting the functional or structural integrity of synapses and their study has become an exciting research topic. Several aspects about the mode of action of these pathogenic autoantibodies remain unsolved, such as their accumulation in specific brain regions. An important factor for this preferential retention could be the influence of brain extracellular space (ECS), a component of the brain that has remained largely inaccessible for exploration due to its complex organization and technical limitations for its examination in living tissue. Recent advances in Nanotechnology and Biotechnology have given rise to unique tools to tackle the study of complex biological systems, thus we are now in a privileged position to explore the architecture of the ECS and the dynamics of CNS autoantibodies into brain tissue. The aim of this project is to define how the dynamics of CNS autoantibodies is affected by the ECS architecture in specific brain regions. This goal will be accomplished by using an original strategy combining classical imaging approaches to map the distribution of CNS autoantibodies between different brain structures and nanoparticle monitoring techniques to visualize at the nanoscopic scale the dynamics of CNS autoantibodies and the ECS architecture.