Tesi etd-05032018-124521
Link copiato negli appunti
Tipo di tesi
Perfezionamento
Autore
AGRIMI, JACOPO
URN
etd-05032018-124521
Titolo
Nutraceutical Approach to Prevent Work Stress-induced Brain-Heart Axis Dysfunction linked to Cardiovascular Disease Risk: A Translational Study
Settore scientifico disciplinare
MED/11
Corso di studi
SCIENZE MEDICHE - Translational Medicine
Commissione
relatore LIONETTI, VINCENZO
Membro Dott.ssa MASTORCI, FRANCESCA
Membro Prof. TUANA, BALWANT
Relatore Prof. CALEO, MATTEO
Membro Dott.ssa MASTORCI, FRANCESCA
Membro Prof. TUANA, BALWANT
Relatore Prof. CALEO, MATTEO
Parole chiave
- Brain-heart
- epigenetics
- nutraceutical
- obesity
- stress
Data inizio appello
29/06/2018;
Disponibilità
completa
Riassunto analitico
Dr. Agrimi’s Ph.D project aimed to validate the hypothesis that the long-term intake of barley (1-3) β-D-Glucan could prevents the onset of brain-heart axis (BHA) dysfunctions induced by the co-exposure to obesity and stress.
It is known that the combined exposure to psychosocial stress (PSS) and high fat diet (HFD), common environmental factors that affect the health of working populations, enhances the vulnerability to metabolic syndrome, insulin resistance, cardiovascular, neurological and psychological disorders (Soufer et al.,2009; Alosco et al., 2014). To date, the prevention of the simultaneous onset of these complex disorders is challenging because effective approaches are lacking. Recent studies have demonstrated that the consumption of a proactive epigenetics diet can optimize vascular, metabolic, and brain health in the community (Chiu et al., 2014). A first study has shown that the chronic exposure of human endothelial cells to 3% of Barley (1-3) β-D-Glucan (BBG) increases the acetylation of histone H4 and the expression of MnSOD, an important enzyme with anti-oxidant and proangiogenic properties, in the presence of oxidative stress (Agostini et al., 2015). A most recent work has demostrated that the long-term intake of standard diet supplemented with pasta containing barley (1-3) β-D-Glucan (P-BBG) induces neovascularization-mediated post-ischemic cardioprotection through endothelial upregulation of VEGF and Parkin in mice (Casieri et al., 2017).
According to these assumptions, the specific aims of my research work were: (a) to develop a murine model of BHA dysfunction induced by the synergistic exposure to HFD and PSS; (b) to test the protective role of diet enriched with BBG in delaying the onset of BHA dysfunction in mice; (c) to define the mechanisms underlying the BBG-induced BHA protection in a cardiac selective knockout mice for brain-derived neurotrophic factor/TrkB signaling.
Thirty wild-type and fifteen cardiac selective TrkB -/- male C57BL/6 mice were fed with three different eperimental diets for 18 weeks: 1) standard diet (SD; 10% Kcal from fat; n=8), 2) HFD (58% Kcal from fat; n=8) or 3) HFD for 8 weeks and then it was supplemented with 3% w/v β-D-glucan (HFD+BG; 58% Kcal from fat; n=8). From the 16th to the 18th week all animals underwent to an established PSS test (resident/intruder). Along all the diet, weight gain and food intake have been evaluated. Before and at the end of the diet glucose plasma level was monitored trough Intraperitoneal Glucose Tolerance Test. At the end of the diet, before and after the two weeks of PSS test: (a) the anxiety-related behavior and the spatial working memory were evaluated by Elevated Plus Maze, Open Field and Y-maze test; (b) Cardiac function was assessed trough echocardiographic analysis. Before the sacrifice load-independent cardiac function was evaluated trough pressure-volume (P-V) loops. At the end of the experiment the following analysis was performed on plasma and tissues (heart and brain): (a) ELISA for BDNF circulating levels, (b) Western blot for cardiac and hippocampal BDNF and TrkB levels, (c) Electron Paramagnetic Resonance (EPR) for detecting ROS levels in the left ventricle.
It is known that the combined exposure to psychosocial stress (PSS) and high fat diet (HFD), common environmental factors that affect the health of working populations, enhances the vulnerability to metabolic syndrome, insulin resistance, cardiovascular, neurological and psychological disorders (Soufer et al.,2009; Alosco et al., 2014). To date, the prevention of the simultaneous onset of these complex disorders is challenging because effective approaches are lacking. Recent studies have demonstrated that the consumption of a proactive epigenetics diet can optimize vascular, metabolic, and brain health in the community (Chiu et al., 2014). A first study has shown that the chronic exposure of human endothelial cells to 3% of Barley (1-3) β-D-Glucan (BBG) increases the acetylation of histone H4 and the expression of MnSOD, an important enzyme with anti-oxidant and proangiogenic properties, in the presence of oxidative stress (Agostini et al., 2015). A most recent work has demostrated that the long-term intake of standard diet supplemented with pasta containing barley (1-3) β-D-Glucan (P-BBG) induces neovascularization-mediated post-ischemic cardioprotection through endothelial upregulation of VEGF and Parkin in mice (Casieri et al., 2017).
According to these assumptions, the specific aims of my research work were: (a) to develop a murine model of BHA dysfunction induced by the synergistic exposure to HFD and PSS; (b) to test the protective role of diet enriched with BBG in delaying the onset of BHA dysfunction in mice; (c) to define the mechanisms underlying the BBG-induced BHA protection in a cardiac selective knockout mice for brain-derived neurotrophic factor/TrkB signaling.
Thirty wild-type and fifteen cardiac selective TrkB -/- male C57BL/6 mice were fed with three different eperimental diets for 18 weeks: 1) standard diet (SD; 10% Kcal from fat; n=8), 2) HFD (58% Kcal from fat; n=8) or 3) HFD for 8 weeks and then it was supplemented with 3% w/v β-D-glucan (HFD+BG; 58% Kcal from fat; n=8). From the 16th to the 18th week all animals underwent to an established PSS test (resident/intruder). Along all the diet, weight gain and food intake have been evaluated. Before and at the end of the diet glucose plasma level was monitored trough Intraperitoneal Glucose Tolerance Test. At the end of the diet, before and after the two weeks of PSS test: (a) the anxiety-related behavior and the spatial working memory were evaluated by Elevated Plus Maze, Open Field and Y-maze test; (b) Cardiac function was assessed trough echocardiographic analysis. Before the sacrifice load-independent cardiac function was evaluated trough pressure-volume (P-V) loops. At the end of the experiment the following analysis was performed on plasma and tissues (heart and brain): (a) ELISA for BDNF circulating levels, (b) Western blot for cardiac and hippocampal BDNF and TrkB levels, (c) Electron Paramagnetic Resonance (EPR) for detecting ROS levels in the left ventricle.
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