Invited Research Meeting - The link between early life adversities and mental disorders

Mercoledì 17 Gennaio 2024, ore 13 Edificio Asclepio U8-Aula 6

Host: Prof Laura Musazzi

♦ Webex per collegamento remoto

The link between early life adversities and mental disorders: from neurobiological mechanisms and circuits to therapeutic intervention.

Exposure to early in life adversities represents one of the most relevant conditions linked to the etiology of
mental disorders. Adverse perinatal events are associated with profound epigenomic and transcriptomic changes in the progeny, which often become manifest during the transition between adolescence and adulthood. With this regard, animal models are particularly useful to investigate the molecular and functional mechanisms that are persistently affected after exposure to early life stress (ELS) and that may represent important targets for pharmacological interventions. In our studies, we employed the prenatal stress (PNS) model in rats to investigate the behavioral and molecular alterations that develop because of this adverse experience. We characterized the progenies at different developmental stages at behavioral and functional
level, also considering sex differences.
I will show that PNS exposure produces emotional dysregulation in male and female adolescent offspring,
including anhedonia, increased anxiety and impaired sociability and some of these alterations persist into adulthood. Interestingly, by integrating the behavioral data, we were able to identify animals that were vulnerable o resilient to the adverse experience during pregnancy. I will also show data on the differential responsiveness to acute challenges of animals pre-exposed to PNS and how pharmacological intervention during the peri-pubertal period may be able to counteract some of the alterations observed in PNS animals.
At the molecular level, whole genome as well as candidate gene analyses were performed in different brain regions to identify mechanisms that may be relevant for the behavioral phenotypes observed in animals exposed to PNS. We also performed cross-species analyses to prioritize genes or systems that are relevant for the long-term alterations that develop following the traumatic experience early in life.
All in all, the characterization of the neurobiological mechanisms contributing to resilience or vulnerability to stress can be instrumental to identify mechanisms that may be targeted by therapeutic approaches to counteract specific pathologic domains that are shared among different mental disorders.

Full Professor of Pharmacology at DISFEB, University of Milan and Senior Investigator at IRCCS Fatebenefratelli, Brescia. He has been Deputy Director of DISFEB (2014-2017) and Coordinator of the Degree course in Pharmacy, University of Milan (2017-2023). He is author of 249 Peer-Reviewed Publications and several chapters of books or Congress proceedings,
with a H-index (Web of Science) of 63 and a Total Number of Citations of >12,000. He is member of different scientific societies, and he is (or has been) recipient of grants from Italian and foreign Agencies, as well as from pharma industries.
Prof. Riva’s research activity is focused on different aspects related to mental disorders including: molecular, functional, and behavioral characterization of animal models for psychiatric disorders, with a major focus on the role of neurodevelopment in shaping the susceptibility to mental illness; Identification of the molecular underpinnings of stress response and their role in the susceptibility or resilience to psychopathology;
Characterization of the mechanisms underlying the action of psychotropic drugs.