CHARACTERISATION OF THE REWARD SYSTEM IN AUTISM (Q3145671)
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Project Q3145671 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | CHARACTERISATION OF THE REWARD SYSTEM IN AUTISM |
Project Q3145671 in Spain |
Statements
66,550.0 Euro
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133,100.0 Euro
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50.0 percent
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1 January 2019
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31 December 2021
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UNIVERSIDAD DEL PAIS VASCO/EUSKAL HERRIKO UNIBERTSITATEA
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48054
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EL TRASTORNO DEL ESPECTRO AUTISTA ES UN TRASTORNO DEL NEURODESARROLLO CARACTERIZADO POR DEFICITS EN LA COMMUNICATION E INTERACTION SOCIAL JUNTO CON COMPORTAMIENTOS REPETITIVOS E INTERESES RESTRINGIDOS Y AFECTA A 1 DE CADA 59 NIÑOS. HASTA LA FECHA NO EXISTEN TRATAMIENTOS FARMACOLOGICOS QUE TRATEN LOS SINTOMAS PRINCIPALES DE LA ENFERMEDAD Y LOS TRATAMIENTOS ACTUALES SE CENTRAN SOBRE TODO EN LA TERAPIA COMPARTMENTAL Y EN EL USO DE MEDICAMENTOS APROBADOS PARA TRATAR OTRAS ENFERMEDADES MENTALES (SOBRE TODO ANTIPSICOTICOS) QUE REDUCEN LOS SINTOMAS ASOCIADOS PERO NO MEJORAN LOS DEFICITS SOCIALES. ESTUDIOS EN HUMANOS Y ANIMALES SOBRE LAS BASES NEUROBIOLOGICAS DEL COMPORTAMIENTO SOCIAL INDICAN QUE EXISTE UNA RED DE CIRCUITOS NEURONALES QUE CONTINUAMENTE INTEGRAN ESTIMULOS SOCIALES Y AMBIENTALES PARA GUIAR LA RESPUESTA SOCIAL MAS ADECUADA A CADA MOMENTO. ENTRE ESTAS VIAS NEURONALES, ES ESPECIALMENTE INTERESANTE EL CIRCUITO MESOLIMBICO, TRADICIONALMENTE IMPLICADO EN MODULAR LA RECOMPENSA Y MOTIVACION. LAS INTERACCIONES SOCIALES POSITIVAS SE CONSIDERAN UNA RECOMPENSA PARA ESPECIES SOCIALES Y SE SABE QUE LOS CIRCUITOS NEURONALES QUE LA MODULAN SON LOS MISMOS QUE LOS QUE MUDAN OTROS ESTIMULOS GRATIFICANTES. EL SISTEMA MESOLITICO CONSISTE EN UNA POBLACION DE NEURONAS LOCALIZADAS EN EL AREA VENTRAL TEGMENTAL QUE EXPRESAN EL NEUROTRANSMISOR DOPAMINA Y PROYECTAN A NEURONAS LOCALIZADAS EN EL NUCLEO ACUMBENS. ESTUDIOS DE RESONANCIA MAGNETICA EN HUMANOS QUE DETECTAN UNA ACTIVACION DIFERENCIAL DE DETERMINADAS ESTRUCTURAS DEL CEREBRO DURANTE LA PRESENTACION DE ESTIMULOS DE CARACTER SOCIAL INDICAN QUE EL NUCLEO ACUMBENS ES UNA ESTRUCTURA CLAVE EN LA MODULACION DE LA RECOMPENSA SOCIAL (DESEO DE BUSCAR RELACIONES SOCIALES). ALGUNAS TEORIAS SUGIEREN QUE LOS DEFICITS EN LA CONDUCTA SOCIAL QUE PRESENTAN LOS INDIVIDUOS CON AUTISMO SE DEBEN A QUE NO ENCUENTRAN LAS INTERACCIONES SOCIALES GRATIFICANTES. LOS MODELOS ANIMALES DAN LA OPORTUNIDAD DE ESTUDIAR A FONDO LOS CIRCUITOS NEURONALES QUE CODIFICAN ESTOS ESTIMULOS. NUESTROS RESULTADOS PRELIMINARES INDICAN QUE EN UN MODELO DE RATON DE AUTISMO EL SISTEMA MESOLITICO ESTA ALTERADO DURANTE TESTS DE INTERACCION SOCIAL, DE TAL MANERA QUE RESULTA EN EVITAR TALES INTERACCIONES EN LUGAR DE INCENTIVARLAS. ESTE PROYECTO PRETENDE CARACTERIZAR ESTE SISTEMA MESOLITICO EN EL MODELO ANIMAL TANTO EX VIVO COMO IN VIVO, CON EL OBJETIVO ULTIMO DE IDENTIFICAR VIAS AFECTADAS QUE PUEDAN SER DIANA FARMACOLOGICA. (Spanish)
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AUTISM SPECTRUM DISORDER (ASD) IS A NEURODEVELOPMENTAL DISORDER CHARACTERIZED PRIMARILY BY IMPAIRED SOCIAL COMMUNICATION AND REPETITIVE BEHAVIORS/RESTRICTED INTERESTS AND, ACCORDING TO THE LATEST LARGESCALE PREVALENCE SURVEY, AFFECTS 1 IN 59 CHILDREN. TO DATE, NO TARGETED PHARMACOTHERAPIES HAVE BEEN DEVELOPED TO ALLEVIATE THE CORE SYMPTOMS OF THE DISEASE AND CURRENT TREATMENTS LARGELY INVOLVE BEHAVIORAL THERAPY AND THE USE OF MEDICATION APPROVED FOR TREATING OTHER MENTAL DISORDERS (MAINLY ATYPICAL ANTIPSYCHOTICS), THAT HELP REDUCE ASSOCIATED SYMPTOMS BUT DO NOT TARGET THE CORE SOCIAL DEFICITS. RESEARCH INTO THE NEUROBIOLOGICAL BASIS OF SOCIAL BEHAVIOR FROM BOTH HUMAN AND ANIMAL STUDIES CONVERGE ON THE EXISTENCE OF A HIGHLY CONSERVED NEURAL NETWORK OF CORTICAL AND SUBCORTICAL STRUCTURES THAT CONTINUOUSLY INTEGRATE SOCIAL AND ENVIRONMENTAL CUES TO GUIDE THE APPROPRIATE BEHAVIORAL RESPONSE AT ANY GIVEN MOMENT. WITHIN THESE PATHWAYS, THE MESOLIMBIC CIRCUIT, TRADITIONALLY IMPLICATED IN ENCODING REWARD AND MOTIVATION, IS RECEIVING SPECIAL ATTENTION. NON-THREATENING SOCIAL INTERACTIONS ARE CONSIDERED A NATURAL REWARD FOR SOCIAL SPECIES AND EVIDENCE FROM BOTH HUMAN AND ANIMAL STUDIES INDICATES THAT SOCIAL REWARD (I.E. DRIVE TO SEEK SOCIAL CONTACT) IS PROCESSED WITHIN THE SAME NEURONAL NETWORK AS NON-SOCIAL REWARDING STIMULI (E.G. MONEY, FOOD, DRUGS OF ABUSE). THE MESOLIMBIC SYSTEM ENTAILS A POPULATION OF NEURONS LOCATED IN THE VENTRAL TEGMENTAL AREA (VTA) THAT EXPRESS THE NEUROTRANSMITTER DOPAMINE (DA) AND PROJECT TO NEURONS LOCATED IN THE NUCLEUS ACCUMBENS (NACC), ALSO REFERRED TO AS THE VENTRAL STRIATUM. IN FACT, HUMAN FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) STUDIES THAT DETECT DIFFERENTIAL ACTIVATION OF SPECIFIC BRAIN REGIONS DURING EXPOSURE TO SOCIAL STIMULI POINT TO THE NACC AS THE KEY STRUCTURE PROCESSING SOCIAL REWARD. SOME THEORIES SUGGEST THAT THE SOCIAL COGNITIVE DEFICITS THAT CHARACTERIZE ASD REFLECT DECREASED MOTIVATION TO ENGAGE IN RECIPROCAL SOCIAL BEHAVIORS BECAUSE INDIVIDUALS WITH AUTISM DO NOT FIND SOCIAL INTERACTIONS REWARDING. ANIMAL STUDIES PROVIDE THE OPPORTUNITY TO EMPLOY INVASIVE TECHNIQUES, INAPPLICABLE TO HUMANS, IN A CONTROLLED RESEARCH ENVIRONMENT MIMICKING, TO A CERTAIN DEGREE, REAL-LIFE EXPERIENCES FOR THE ANIMAL, THEREBY ALLOWING FOR IN DEPTH INVESTIGATION OF THE SPECIFIC CIRCUITS AND MOLECULAR MECHANISMS THAT MODULATE SOCIAL BEHAVIOR. OUR PRELIMINARY DATA INDICATE THAT THE FUNCTIONING OF THE MESOLIMBIC DOPAMINE SYSTEM DURING SOCIAL INTERACTION IS AFFECTED IN A MOUSE MODEL OF AUTISM, IN SUCH A WAY THAT ENCODES AVOIDANCE RATHER THAN APPROACH BEHAVIOR. THE PRESENT PROJECT AIMS AT CHARACTERIZING THIS SYSTEM BOTH EX VIVO AND IN VIVO, WITH THE GOAL OF IDENTIFYING AFFECTED PATHWAYS THAT COULD BE PHARMACOLOGICALLY TARGETABLE. (English)
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Leioa
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Identifiers
RTI2018-101427-B-I00
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