Menu
MapConnectionsTopicsBulgariaThe Night (K-TRIO)Marie Skłodowska-CurieFor studentsFor teachersMethodologySurprise me
HEIndividual fellowship2023–2025

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

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-09-01 → 2025-08-31
EU contribution
€230,774
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

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

Post-traumatic stress disorder (PTSD) remains a major mental health challenge worldwide, often accompanied by comorbid depression and cognitive impairments. Patients with comorbid forms are the ones with the poorest prognosis and treatment response. However, it remains unknown how traumas lead to the development of depression. This is in part caused by current limitations of our preclinical models, which are unable to resemble comorbid forms of PTSD and do not differentiate between adaptive fear (useful for survival) and maladaptive fear (leading to pathology). This project was designed to address both challenges. We aimed to develop a new experimental approach that overcomes these limitations. In addition, we aimed to identify the neural circuits and cellular mechanisms that underlie the transition from adaptive to maladaptive fear, and to explore how these processes may drive comorbid depression. Specifically, the project focused on hippocampal engrams, the cellular ensembles that store fear memories. We investigated how engrams encoding maladaptive fear mediate depression related behaviors. By exploring the distribution, composition, and molecular fingerprint of these maladaptive engrams, this project elucidates a potential mechanism explaining how trauma induces depression-related symptoms, potentially discovering new targets for treatment development.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • AARHUS UNIVERSITET · Aarhus CCoordinatorDenmark

Links

Data: CORDIS, © European Union