Leader: Laura Ballerini (SISSA); Other collaborator(s):
As in mammals, zebrafish age-related changes in synaptic integrity correlate to cognitive decline, allowing to target fundamental mechanisms of aging and identify pro-healthy aging interventions. We will investigate brain aging by evaluating synaptic integrity and physiological features by live imaging, electrophysiology and behaviour. By biochemistry approaches we will focus on proteins involved in age-related disorders (i.e. neurodegenerative diseases) such as the zebrafish homologues of prion proteins and synucleins. We will combine aging to stress factors, such as fear and anxiety. The impact of age and environmental variables on motor behaviour, sensory-driven decisions and the underlying neuronal/synaptic processes will be investigated by machine learning tools and information theoretical approaches
Brief description of the activities and of the intermediate results: SISSA recruited a technologist with senior research experience (Dr. Giada Cellot) to coordinate the project research developments involving the zebrafish animal model and facility. We are investigating the influence of aging and synaptic senescence in the responses to stress factor, by exploiting social deprivation paradigms. To this aim, in zebrafish exposed to physiological and to stress conditions (one week of social isolation) we evaluated both physiological features (in vivo) and the synaptic integrity (ex vivo) in juvenile, adult and aged zebrafish, combining behavioral analysis with confocal microscopy of dendritic spine reconstruction. We reported modifications in the social preference of zebrafish during aging, with a progressive transition from social to antisocial behavior, associated with clear, age-related, decrease in the sensitivity to social isolation. Such a decreased sensitivity resulted in reduced anxiety responses, ultimately leading to social preference reshaping in aged zebrafish, when compared to juvenile ones. We refined machine learning tools to improve the level of sophistication of behavioral analysis and to quantify complex aspects of age and stress related behavior modifications. A preliminary histological analysis suggested that these behavioral changes are correlated to age-related modifications in the synaptic plasticity of neuronal networks associated to anxiety and social responses.
Our contribution was selected for the Age-It General Meeting, Ca' Foscari Venice, May 20-22, 2024: Aging affects social preference and anxiety responses in zebrafish, authored by Giada Cellot, Safaa Mamoun Abdelmageid Ali, Audrey Franceschi Biagioni, Anna Burato, Giuseppe Legname, Davide Zoccolan, Laura Ballerini
From April 2024 to September 2024 we implemented the number of animals tested at all ages (2, 12, 20 months) and thanks to the developed machine learning analysis we confirmed a statistical significant change of social behavior during aging including for the first time analysis of parameters which specify inter-individual social interactions at unprecedent levels. Full histological testing is now undergoing to correlate neural circuit morphological adaptation to such changes, in particular those involved in anxiety responses. We are now setting useful protocols to correlate circuit changes, sustaining behavioral modifications during aging, to synaptic molecular profiles.
We increased sample size of our behavioral experiments and further improved their kinematic analysis through deep learning tools. Additionally, immunofluorescence staining of synaptic markers in brains obtained in different experimental conditions (i.e. isolation/not isolation, young/adult/aged animals) is undergoing to explore the mechanistic insight of the observed changes.
Coming soon