Project ID NS-MH2023_44


Co Supervisor 1A IoPPN/Psychological MedicineWebsite

Co Supervisor 1B IoPPN/Psychological MedicineWebsite

Additional Supervisor Alessandra Borsini

Cellular models to identify causal molecular mechanisms of early life stress (ELS)-Induced comorbidity

In this project we will use a coherent in vitro, experimental, systematic approach, to mimic early-life stress (ELS)-relevant cortisol and inflammatory insults on cells from the human brain, heart, liver, pancreas and blood immune system, to identify mechanisms underpinning the relationship between ELS and unipolar depression, coronary heart disease and diabetes type II. We have successfully used such in vitro approaches before (see publications).

The project consists of three main aims:
Aim 1. Mimic ELS-related insults in human cells derived from brain, heart, liver, pancreas, adipose tissue and immune system (Year 1 of PhD), using both cortisol and the pro-inflammatory cytokine, interleukin-1 beta, and study the effects on specific hypothesis-driven functional and biochemical mechanisms underlying the aforementioned disorders.
Aim 2. Modulate the functional and biochemical cellular mechanisms induced by the stress-related insults identified in Aim 1 (Year 2-3): We will activate or inhibit the identified mechanisms (from Aim 1), using treatment with pharmacological drugs that can stimulate or inhibit such pathways.

Techniques and skills that will be learnt:

Cell culture of a variety of human cell lines derived from brain (hippocampal progenitor cell line HPC03A/07 and hypothalamic neurons derived from iPSCs), and primary cells from heart, liver, pancreas and blood immune system (respectively, cardiomyocytes, hepatocytes, pancreatic cells EndoC-βH and peripheral blood mononuclear cells);

Immunostaining for the quantification of neuronal, glial and apoptotic cells;

Single and multiplex platforms (ELISA and Meso Scale Discovery assay) for proteins level quantification; qPCR for mRNA gene expression analysis.

Representative Publications

Anacker C, Cattaneo A, Musaelyan K, Zunszain PA, Horowitz M, Molteni R, Luoni A, Calabrese F, Tansey K, Gennarelli M, Thuret S, Price J, Uher R, Riva MA, Pariante CM. Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8708-13.

Borsini A., Nicolaou N., Camacho-Muñoz D., Kendall A. C., Di Benedetto M. G., Giacobbe J., Su K., Pariante C. M. Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis. Molecular Psychiatry. 2021 [Epub ahead of print].

Cattaneo A, Cattane N, Malpighi C, Czamara D, Suarez A, Mariani N, Kajantie E, Luoni A, Eriksson JG, Lahti J, Mondelli V, Dazzan P, Räikkönen K, Binder EB, Riva MA, Pariante CM. FoxO1, A2M, and TGF-β1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses. Molecular Psychiatry. 2018 Nov;23(11):2192-2208.