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PID2020-115896RJ-I00

Financiado

MATRIX-MICROGLIA INTERACTIONS IN THE AGING BRAIN

NEUROLOGICAL DISORDERS ARE A GROWING CAUSE OF MORTALITY AND LEADING CAUSE OF DISABILITY, CARRYING GREAT SOCIO-ECONOMIC BURDEN AND IMPAIRING THE ELDERLY LIFE OF MILLIONS. THE OUTSTANDING SCIENTIFIC ACHIEVEMENTS FROM RECENT DECADES... ver más

01/01/2020

UPV

198K€

Presupuesto del proyecto: 198K€

Líder del proyecto

UNIVERSIDAD DEL PAIS VASCO/EUSKAL HERRIKO UNI... No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 45

Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2020-01-01 No tenemos la información de la convocatoria

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Líder del proyecto

UNIVERSIDAD DEL PAIS VASCO/EUSKAL HERRIKO UNI... No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 45

Presupuesto del proyecto 198K€

Descripción del proyecto NEUROLOGICAL DISORDERS ARE A GROWING CAUSE OF MORTALITY AND LEADING CAUSE OF DISABILITY, CARRYING GREAT SOCIO-ECONOMIC BURDEN AND IMPAIRING THE ELDERLY LIFE OF MILLIONS. THE OUTSTANDING SCIENTIFIC ACHIEVEMENTS FROM RECENT DECADES HAVE EXTENDED OUR LIFE EXPECTANCY CONSIDERABLY, STRETCHING THE LIFESPAN OF THE POPULATION AND THEREFORE THE INCIDENCE OF AGE-RELATED PATHOLOGIES, ESPECIALLY BRAIN DISORDERS. THE EXPONENTIAL PROGRESS IN BIOMEDICINE HAS NOT BEEN FOLLOWED BY SIGNIFICANT ADVANCES IN NEURODEGENERATIVE DISEASES, WITH LIMITED SUCCESS IN TRANSLATING INSIGHTS FROM ANIMAL MODELS INTO HUMAN-TARGETED THERAPIES. THIS IS PARTLY DUE TO MOST INVESTIGATIONS BEING PERFORMED IN YOUNG ANIMALS, WHILE NEUROPATHOLOGY OCCURS MOSTLY IN OLD INDIVIDUALS. BEYOND NEURONS AND GLIA, THE BRAIN HOLDS A DYNAMIC SCAFFOLD KNOWN AS THE EXTRACELLULAR MATRIX, WHICH BUILDS UP THROUGHOUT LIFE AND FUNCTIONS AS CELL-ATTACHING FRAMEWORK AND SIGNALING HUB. MICROGLIA, THE NEVER-RESTING IMMUNE CELLS OF THE CNS, DYNAMICALLY SURVEY THE BRAIN PARENCHYMA SCANNING THE EXTRACELLULAR MICROENVIRONMENT AND ORCHESTRATING THE RESPONSE TO INJURY. WE HAVE RECENTLY DESCRIBED IN ADULT PARKINSONIAN MICE A BIDIRECTIONAL LOOP BETWEEN HYALURONAN, THE MAIN COMPONENT OF THE NEURAL MATRIX, AND MICROGLIA, WHICH AFFECTS BOTH MATRIX STRUCTURE AND MICROGLIA ACTIVATION, WITH CONSEQUENCES ON NEURODEGENERATION. DESPITE REPORTED ACCUMULATION OF HYALURONAN IN THE AGING BRAIN, AND PROVEN EFFECT OF MATRIX STIFFNESS ON THE PHYSIOLOGY, MOTILITY AND MIGRATION OF BRAIN CELLS, IT IS UNKNOWN WHETHER AGE-RELATED CHANGES IN THE STRUCTURAL MATRIX AFFECT MICROGLIAL DYNAMICS OR REACTIVE STATE. HERE WE PROPOSE TO STUDY, IN YOUNG, ADULT AND AGED MICE, THE FUNCTIONAL INTERACTION BETWEEN THE HYALURONAN MATRIX AND MICROGLIA DYNAMICS. WE WILL USE STATE-OF-THE-ART TECHNIQUES, SUCH AS IN VIVO TWO-PHOTON TIME-LAPSE IMAGING IN YOUNG AND AGED MICE TO DETERMINE MICROGLIAL PROCESS MOTILITY AND RESPONSE TO INJURY UNDER DIFFERENT PARADIGMS OF HYALURONAN MODIFICATION. MICROGLIAL REACTIVE STATE AND PHAGOCYTOSIS WILL BE EVALUATED IN VIVO IN FIXED TISSUE BY CONFOCAL MICROSCOPY AND IN 3D-IN VITRO CULTURES BY LIVE CELL IMAGING VIA SCRIPT-AIDED IMAGE ANALYSIS. THIS PROJECT, THE FIRST OF THE PI AS AN INDEPENDENT RESEARCHER, WILL HELP UNDERSTAND HOW THE BRAIN RESPONDS TO INJURY IN AGING, PAVING THE WAY TO EXPLORE GLIA-MATRIX INTERACTIONS IN THE AGING BRAIN, A STEPPING-STONE IN THE LONG-TERM EFFORT TOWARDS UNDERSTANDING AND MITIGATING NEURODEGENERATION. ICROGLIA\IMAGING\GLIA\3D CULTURES\IN VIVO\HYALURONAN\IMAGE ANALYSIS\TWO-PHOTON MICROSCOPY\AGING\EXTRACELLULAR MATRIX

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