PB0505 - Relation among Brain Derived Neurotrophic Factor, depression, and extracellular vesicles-derived miRNA – results from an Italian cohort

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Silvia Stella Barbieri, PhD

Head of the Brain-Heart Axis Unit
Centro Cardiologico Monzino IRCCS
Milan, Lombardia, Italy

Co-Author(s)

PA

Patrizia Amadio

Senior Scientist at the Heart and Brain Axis Unit
Centro Cardiologico Monzino IRCCS
Milan, Lombardia, Italy
CM

Chiara Macchi

Researcher Assistant Professor at Department of Biomolecular and Pharmacological Sciences
Università degli Studi di Milano
Milan, Lombardia, Italy
MZ

Marta Zarà

Researcher at the Brain-Heart Axis Unit
Centro Cardiologico Monzino IRCCS
Milan, Lombardia, Italy
CF

Chiara Favero

Senior Scientist at EPIGET LAB, Department of Clinical Sciences and Community Health
Università degli Studi di Milano
Milan, Lombardia, Italy
GS

Giulia Solazzo

PhD Student at EPIGET LAB, Department of Clinical Sciences and Community Health
Università degli Studi di Milano
Milan, Lombardia, Italy
LV

Luisella Vigna

Medical Doctor at Occupational Health Unit
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Lombardia, Italy
MG

Maria Francesca Greco

PhD Student at the 2Department of Biomolecular and Pharmacological Sciences
Università degli Studi di Milano
Milan, Lombardia, Italy
MB

Massimiliano Buoli

Professor at the Department of Pathophysiology and Transplantation
Università degli Studi di Milano
Milan, Lombardia, Italy
CS

Cesare R Siroti

Emeritus Professor at the Department of Biomolecular and Pharmacological Sciences
Università degli Studi di Milano
Milan, Lombardia, Italy
AI

Alessandro Ieraci

Researcher Assistant Professor at Department of Pharmaceutical Sciences
Università degli Studi di Milano
Milan, Lombardia, Italy
MR

Massimiliano Ruscica

Associate Professor at Department of Biomolecular and Pharmacological Sciences
Università degli Studi di Milano
Milan, Lombardia, Italy
VB

Valentina Bollati

Associate Professor at EPIGET LAB, Department of Clinical Sciences and Community Health
Università degli Studi di Milano
Milan, Lombardia, Italy

Background: Obesity and depression are intertwined diseases often associated with increased risk of cardiovascular (CAD) complications. Despite modifications in the Brain-Derived Neurotrophic Factor (BDNF) levels in the brain have been observed in subjects with depression and obesity, the relationships among peripheral BDNF, depression and obesity are not well-defined, yet. Changes in extracellular vesicle (EV)-derived miRNAs in blood have been related to obesity, depression and CAD.

Aims: In this study, we investigated the association among BDNF, depression and EV-derived miRNAs related to atherothrombosis.

Methods: 743 overweight/obese individuals (BMI>25 kg/m2) of the SPHERE cohort were analyzed. A standard biochemical evaluation was assessed. BDNF plasma levels were measured by ELISA, EV-miRNA isolated from plasma and analysed by TaqMan™ OpenArray™. Depression state was evaluated by the Beck Depression Inventory-II (BDI-II).

Results: In multivariate analysis, a negative association between BDNF and depression was found (p=0.0004), and this relationship was modified by the high levels of inflammatory marker IF1, suggesting that a potential protective activity of BDNF is dependent on the high inflammatory levels. From the analysis of EV-derived miRNAs emerged a clear that BDNF associated with about 80 upregulated and 59 downregulated miRNAs known to be related to cardiovascular diseases. miRNA target analysis showed that 18 of these genes fall in the atherothrombotic dataset. Interestingly, a network between genes involved in coagulation and inflammation specifically PTGS2, MTHFR, TNF-a, IL6, IL1b, SERPIN1, PLAT, TFPI, TF and BDNF was found.

Conclusion(s): Overall these data provide a robust association among depression score, obesity, indicating and BDNF plasma levels, and support the hypothesis of a critical link between circulating BDNF levels and atherothrombotic risk.