Type 2 Diabetes Mellitus and Parkinson's Disease: investigation of metabolic profile, neuroinflammation, neurodegeneration, and motor and non-motor behavior

• Grant number: 23/06350-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosana de Lima Pagano
• Grantee: Ana Carolina Pinheiro Campos
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Type 2 diabetes mellitus (DM2) is one of the most prevalent non-communicating diseases today, characterized by acquired insulin resistance. On the other hand, Parkinson's disease (PD) is the third most prevalent neurodegenerative disease in the world, being characterized by the progressive death of dopaminergic neurons in the nigrostriatal pathway, compromising the motor circuitry. Despite appearing to be disorders with completely different etiologies, recently, the synergy between DM2 and PD has been widely studied. While DM2 is a risk factor for PD, worsening the motor deficit, individuals affected by PD have impaired glucose metabolism. DM2 and PD share similar biomolecular mechanisms, such as activation of the inflammatory cascade and formation of protein aggregates. Additionally, drugs proposed for the treatment of DM2 have been used in the presence of PD with promising results. However, the biomolecular mechanisms involved in the synergy between the two diseases have not yet been fully elucidated. In this project, we aim to investigate the systemic and central metabolic profile, neuroinflammation, and neurodegeneration in a combined preclinical model of DM2 and PD in rats. Therefore, this project was divided into four scientific challenges: 1) Investigation of the systemic and central metabolic profile, neuroinflammation, and glutamatergic clearance in the presence of the DM2 model induced by a cafeteria diet (obesity) and streptozotocin injections; 2) Investigation of the previously mentioned mechanisms in the presence of DM2 concomitant with PD, induced by the striatal injection of 6-hydroxydopamine; 3) Evaluation of the presence and severity of motor and non-motor symptoms (olfactory loss, cognitive deficit, pain, and anxiety and depression behavior) in the presence of the two models, as well as the modulation of the motor circuitry and formation of protein aggregates and 4) Evaluation of pharmacological treatment with levodopa against motor disorders in both models and the development of the dyskinesia phenomenon in the PD model. We believe that the broad and exploratory investigation of the synergy between DM2 and PD will elucidate the relevant mechanisms that will contribute to the development of new proposals for therapeutic strategies in an attempt to improve the quality of life of individuals affected concomitantly with DM2 and PD. (AU)