Investigation of the effect of diabetes mellitus on basal ganglia modulation: a preclinical study

• Grant number: 25/03822-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Pinheiro Campos
• Grantee: Bianca Rafael Olivares
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Diabetes mellitus is a metabolic disorder with high prevalence worldwide. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, characterized by the presence of peripheral and central insulin resistance, increased hepatic glucose production, and persistent hyperglycemia. T2DM is highly associated with several comorbidities, such as peripheral neuropathy, autonomic neuropathy, cardiac, renal, hepatic, and metabolic disorders, among others, which form what is known as the "ominous octet". These disorders are responsible for high mortality and a negative impact on the quality of life of affected individuals. Preclinical models are essential in an attempt to better understand the effects of T2DM and its possible treatments. One of the greatest risk factors for T2DM is obesity, responsible for regulating fundamental hormones of the appetite response. Therefore, the use of caloric diets combined with low doses of streptozotocin (STZ, a toxic agent that induces the death of insulin-secreting ¿-pancreatic islets) has been routinely used in the literature to mimic the effects of T2DM in rodents. Insulin resistance and persistent hyperglycemia observed in T2DM induce a neuroinflammatory and neurodegenerative response in the central nervous system, leading to associated symptoms such as cerebral microvascular disorders, cognitive deficit, and motor dysfunction. However, the effect of T2DM on the basal ganglia has been little explored. Interest in this association has recently grown since T2DM is a risk factor for Parkinson's disease (PD) and an important comorbidity that leads to increased motor deficits in individuals with PD. Furthermore, normoglycemic drugs generally associated with diabetes treatment have had interesting results in the treatment of PD. Therefore, in this project, we intend to evaluate the effect of DM2 on neuroinflammation in the basal ganglia that are involved in the pathophysiology of PD, as well as the activation pattern of the hypothalamic arcuate nucleus responsible for appetite modulation. We believe that this project will be able to elucidate the central mechanisms of DM2 and its association with motor disorders, including PD.