Neurobiology of Stress

The broad goal of the lab is to understand mechanistically how stress (especially experienced in early life) is encoded at the molecular and structural level to have long-lasting impact on behavior and brain function and how pharmacological and behavioral interventions can rescue stress-induced phenotypes. To tackle this question, we combine different approaches including translational animal models, molecular techniques, morphology, neuropsychopharmacology in a highly interdisciplinary and translational approach. Our long-term goal is to contribute to a more precise understanding of how stress impacts and modulates brain function, so as to ultimately develop more targeted strategies for both prevention and treatment of stress-related mental disorders.

TOPIC 1: Impact of early experience on central nervous system function

This project aims at understanding the effects induced by early life stressful events in the first period of postnatal life and their impact on developing psychatric pathologies later in life. We are carrying out an extensive behavioral characterization using different transgenic animal stairns, molecular analysis on different types of tissues and cell such as brain (human and mice), cerebral spine fluid (human and mice) and isolated cell populations (with a focus on NG2+ cells). With this study, we have already identified molecular targets altered early in life (Treccani et al., 2021) and planning to investigate the causal relationship between those targets and the development of the disease.

TOPIC 2: Decoding the mechanism of fast acting antidepressant drug such as ketamine

 Ketamine is one of the most promising antidepressant drugs already showing successful results in the cure of treatment-resistant depressed patients. However, many questions regarding the action of ketamine remained unsolved particularly the mechanisms by wich ketamine interferes with the process of spine formation and stabilization in the activated neurons and wether the activation/inhibitation of specific brain circuitry is responsible for its action. The overarching aim of this project is to encode molecular pathways and brain circuitry underlying the effects of ketamine by means of transgenic mouse lines, advance transcriptome and in vivo manipulation.

TOPIC 3: Systematic Review

 Recently growing evidence show that lack in preclinical study reproducibility is one of the main factors leading to failure in clinical trials with enormous impact on the process of new drug discovery. This is particularly true for the neurosciences where attrition rates are extremely high. Due the growing awareness of responsible and properly designed animal-based research, we have recently explored the field of systematic review as a powerful tool to enable rigorous, justified and most importantly high translational research. In collaboration with the lab of Prof Marianne Müller, we are conducting a systematic rewiew in the field of intervention promoting resilience in preclinical studies.