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

Descripción del proyecto

Apertura de la caja negra del espacio extracelular

El sistema nervioso central está formado por miles de millones de células. Las membranas celulares crean dos compartimentos clasificados a grandes rasgos como el espacio intracelular y el espacio extracelular. El espacio extracelular ocupa alrededor de una quinta parte del volumen del encéfalo y rellena incluso los espacios más pequeños entre las células. Si bien las células, sus constituyentes, e incluso el movimiento de las sustancias a lo largo de las membranas, se han estudiado ampliamente, el complejo microentorno en 3D que rodea a las células todavía es un confín desconocido en gran medida. NanoPSYCH está utilizando nuevas herramientas de nanotecnología y biotecnología para investigar la estructura del espacio extracelular y, en particular, cómo afecta a la acumulación de autoanticuerpos. Recientemente, se ha relacionado la autoinmunidad a trastornos neuropsiquiátricos y NanoPSYCH espera arrojar luz a los mecanismos neurobiológicos de este tipo de afecciones.

Objetivo

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.