Parkinson's Disease and the Heart: Studying Cardiac Metabolism in the 6-Hydroxydopamine Model.

Parkinson's-disease (PD) is an incurable, age-related neurodegenerative disease, and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient's quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD; however, its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine are the metabolites that significantly discriminate parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, the biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, the glucose-alanine cycle, glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation.

Propolis induces cardiac metabolism changes in 6-hydroxydopamine animal model: A dietary intervention as a potential cardioprotective approach in Parkinson's disease.

While there is sustained growth of the older population worldwide, ageing is a consistent risk factor for neurodegenerative diseases, such as Parkinson's-disease (PD). Considered an emblematic movement disorder, PD comprises a miscellany of non-motor symptoms, for which effective management remains an unfulfilled need in clinical practice. Highlighted are the cardiovascular abnormalities, that cause significant burden in PD patients. Evidence suggests that key biological processes underlying PD pathophysiology can be modulated by diet-derived bioactive compounds, such as green propolis, a natural functional food with biological and pharmacological properties. The effects of propolis on cardiac affection associated to PD have received little coverage. In this study, a metabolomics approach and Positron Emission Tomography (PET) imaging were used to assess the metabolic response to diet supplementation with green propolis on heart outcomes of rats with Parkinsonism induced by 6-hydroxydopamine (6-OHDA rats). Untargeted metabolomics approach revealed four cardiac metabolites (2-hydroxybutyric acid, 3-hydroxybutyric acid, monoacylglycerol and alanine) that were significantly modified between animal groups (6-OHDA, 6-OHDA + Propolis and sham). Propolis-induced changes in the level of these cardiac metabolites suggest beneficial effects of diet intervention. From the metabolites affected, functional analysis identified changes in propanoate metabolism (a key carbohydrate metabolism related metabolic pathway), glucose-alanine cycle, protein and fatty acid biosynthesis, energy metabolism, glutathione metabolism and urea cycle. PET imaging detected higher glucose metabolism in the 17 areas of the left ventricle of all rats treated with propolis, substantially contrasting from those rats that did not consume propolis. Our results bring new insights into cardiac metabolic substrates and pathways involved in the mechanisms of the effects of propolis in experimental PD and provide potential novel targets for research in the quest for future therapeutic strategies.