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ENGRAMS IN TRAUMATIC MEMORY: FINDING NOVEL THERAPEUTIC AVENUES IN DEPRESSION AND PTSD.

Descripción del proyecto

Investigación de nuevos tratamientos para el trastorno por estrés postraumático y la depresión

Los pacientes con trastorno por estrés postraumático (TEPT) tienen más probabilidades de desarrollar una depresión mayor (DM), lo que puede limitar su respuesta al tratamiento y provocar síntomas más graves. La atrofia y la pérdida sináptica en el hipocampo pueden provocar deficiencias en la memoria y el aprendizaje del miedo, que se relacionan tanto con el TEPT como con la DM. Las investigaciones sugieren que la regulación de los glucocorticoides tras un trauma puede repercutir en la consolidación de la memoria. La hipótesis del proyecto PoMAM, financiado con fondos europeos, es que una memoria del miedo inadaptada, resultado de una disfunción del hipocampo, puede contribuir al desarrollo de la DM, explicando así la frecuente coocurrencia del TEPT y la DM. El objetivo del proyecto es proporcionar nuevos conocimientos y metodologías en psicología e identificar dianas terapéuticas.

Objetivo

Despite 70% of people are going to experience a traumatic event throughout life, only 3.9% are going to develop post-traumatic stress disorder (PTSD). Curiously, people who develop PTSD also present a higher risk of developing Major Depressive Disorder (MDD). Thus, 50-70% of PTSD patients will live with a diagnostic of MDD, which in terms of prognosis means poor response to treatment and worse symptomatology. Despite the clinical relevance of this comorbidity, it remains unknown if there are shared molecular mechanisms. Impairments in fear memory and learning were related to PTSD and MDD, in association with atrophy and synaptic loss in the hippocampus (HPC). In turn, the HPC plays a crucial role in fear memory, encoding the contextual information related to the fearful stimulus. Thus, we propose that maladaptive fear memory due to hippocampal dysfunction can also contribute to MDD, explaining the high co-morbidity between PTSD and MDD. Importantly, preclinical research focus on fear memory have provided us with promising knowledge for potential PTSD therapeutics. For instance, the regulation of glucocorticoids in the “golden hours” after trauma to prevent memory consolidation, the use of beta-adrenergic blockers to disrupt consolidated memories, or different psychotherapeutic approaches to enhanced memory extinction. Recently, the advances with chemo- and optogenetic technics have allowed the identification and functional modulation of neurons involved in encoding a specific memory (engrams), thereby allowing a highly refined study of memory substrates. Despite these advances, the use of such approaches in genetic animal models for the study of psychiatric comorbidities is still poorly explored. We believe that this combination can bring new insights and methodological possibilities for the field. In parallel, increase our understanding about the basis of PTSD and MDD can provide new therapeutical targets with direct implications for human health.

Coordinador

AARHUS UNIVERSITET
Aportación neta de la UEn
€ 230 774,40
Dirección
NORDRE RINGGADE 1
8000 Aarhus C
Dinamarca

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Región
Danmark Midtjylland Østjylland
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos