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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

Project description

Opening the black box of extracellular space

The central nervous system is made up of billions of cells. The cellular membranes create two broadly classified compartments, intracellular and extracellular space. Extracellular space occupies about a fifth of brain volume and it fills even the smallest gaps between cells. While the cells, their constituents, and even the movement of substances across the membranes have been widely studied, the complex 3D microenvironment surrounding the cells is still a largely uncharted frontier. NanoPSYCH is using new tools in nanotechnology and biotechnology to investigate the structure of the extracellular space and, in particular, how it affects the accumulation of autoantibodies. Autoimmunity has recently been linked to neuropsychiatric disorders and NanoPSYCH hopes to shed light on neurobiological mechanisms of such conditions.

Objective

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.

Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 196 707,84
Address
RUE MICHEL ANGE 3
75794 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 196 707,84