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BFU2012-31164

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DAÑO Y REPARACION VESTIBULAR EN LA OTOTOXICIDAD CRONICA: ETAPAS CELULARES, DEFIC...

DAÑO Y REPARACION VESTIBULAR EN LA OTOTOXICIDAD CRONICA: ETAPAS CELULARES, DEFICITS FISIOLOGICOS Y MECANISMOS MOLECULARES TOXIC INSULTS TO THE MAMMALIAN VESTIBULAR SYSTEM MAY CAUSE LOSS OF THE SENSORY HAIR CELLS (HCS) AND PERMANENT LOSS OF EQUILIBRIUM. HOWEVER, CHRONIC EXPOSURE MAY CAUSE A PROGRESSIVE APPEARANCE OF THE SYMPTOMS AND THESE MAY THEN SHO... ver más

01/01/2012

94K€

Presupuesto del proyecto: 94K€

Líder del proyecto

UNIVERSIDAD DE BARCELONA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 328

Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2012-01-01

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Líder del proyecto

UNIVERSIDAD DE BARCELONA

Total investigadores 328

Presupuesto del proyecto 94K€

Descripción del proyecto TOXIC INSULTS TO THE MAMMALIAN VESTIBULAR SYSTEM MAY CAUSE LOSS OF THE SENSORY HAIR CELLS (HCS) AND PERMANENT LOSS OF EQUILIBRIUM. HOWEVER, CHRONIC EXPOSURE MAY CAUSE A PROGRESSIVE APPEARANCE OF THE SYMPTOMS AND THESE MAY THEN SHOW VARIABLE DEGREES OF REVERSIBILITY. ANIMAL STUDIES HAVE CHARACTERIZED THE PROGRESSIVE PATHOLOGY ASSOCIATED WITH CHRONIC VESTIBULAR TOXICITY, INCLUDING DAMAGE TO THE AFFERENT NERVE TERMINALS AND HAIR CELL DEMISE BY EXTRUSION FROM THE SENSORY EPITHELIUM, BUT THE CRITICAL STAGES INVOLVED IN THESE PROCESSES, THEIR PHYSIOLOGICAL RELEVANCE, THEIR REVERSIBILITY, AND THEIR MOLECULAR BASIS REMAIN TO BE IDENTIFIED. THIS PROJECT WILL USE OUR PREVIOUSLY DEFINED MODEL OF DRINKING WATER EXPOSURE OF RATS TO 3,3-IMINODIPROPIONITRILE (IDPN), WHICH WILL ALLOW TO ADDRESS THESE QUESTIONS WITH UNPRECEDENTED CAPABILITY. FUNCTIONAL, HISTOLOGICAL (ULTRA-STRUCTURAL AND IMMUNOCONFOCAL) AND MOLECULAR (MRNA AND PROTEIN) DATA WILL BE COLLECTED TO:1. IDENTIFY THE STAGES INVOLVED IN THE DAMAGE AND REPAIR PROCESSES OF THE VESTIBULAR AFFERENTS DURING CHRONIC OTOTOXIC EXPOSURE, AND DETERMINE THEIR FUNCTIONAL RELEVANCE.2. DETERMINE IF THE LOSS OF THE TYPE 1 HC-AFFERENT SEPTATE JUNCTIONS IS SUFFICIENT TO CAUSE THE FUNCTIONAL DEFICITS INDICATIVE OF SYNAPTIC UNCOUPLING IN THE VESTIBULAR SYSTEM.3. DETERMINE THE FATE OF HCS SUFFERING CILIARY COALESCENCE AND THE INITIAL OR MIDDLE STAGES OF EXTRUSION (REPAIR, SURVIVAL AS DAMAGED CELLS, OR DEMISE).4. IDENTIFY MOLECULAR MECHANISMS UNDERLYING THESE DAMAGE AND REPAIR PROCESSES, BY ASSESSING IN THE VESTIBULAR EPITHELIA (HCS, SUPPORTING CELLS AND AFFERENT TERMINALS) AND GANGLIA (VESTIBULAR NEURON CELL BODIES) THE CHANGES IN THE EXPRESSION AND/OR ACTIVITY OF MAIN CANDIDATES (BCL-2 APOPTOSIS REGULATORY GENE FAMILY, BDNF /TRKB, JNK, TIGAR, REELIN AND CELLULAR PRION PROTEIN, CALPAINS, CALCINEURIN, PKA, PKC, CAPRIN1).THE EXPECTED RESULTS SHALL BE OF HIGH RELEVANCE IN THERAPEUTIC, PROPHYLACTIC, AND BASIC BIOLOGY POINTS OF VIEW. THEY ARE OF INTEREST TO A PROMOTER-OBSERVER ENTITY DEVOTED TO DEVELOPING THERAPIES FOR VESTIBULAR DISEASES.

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