Role of bile acid TUDCA in the glucose and energy metabolism of experimental Alzheimer's disease mice model

Author(s)

Lucas Zangerolamo

• Document type: Master's Dissertation
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2021-02-25

Examining board members

Claudio Chrysostomo Werneck; Camila Aparecida Machado De Oliveira

• Advisor: Helena Cristina de Lima Barbosa Sampaio

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation and extracellular deposition of amyloid beta protein, mainly in the hippocampus, resulting in neuronal death and progressive cognitive decline. Studies have shown that central and peripheral insulin resistance, as well as changes in energy metabolism, are also often found in patients and animal models of this disease. Several strategies have been proposed and tested for the treatment of Alzheimer's, among which we highlight the tauroursodeoxycholic bile acid (TUDCA). TUDCA is a bile acid conjugated with taurine and exert neuroprotective properties, reducing inflammatory, apoptotic and endoplasmic reticulum stress markers, in addition to acting in pathways that regulate energy, glucose and lipid metabolism. In APP/PS1 transgenic mice, model of AD, treatment with TUDCA reduces the accumulation of amyloid beta plaques, attenuating the central damages caused by this disease. However, its metabolic effects in an animal model of AD remain unknown. In this work, using the streptozotocin-induced Alzheimer's mice model and treated with 300 mg/Kg of intraperitoneal TUDCA, our objective was to evaluate the effects of this bile acid on the glucose and energetic metabolism of this model, analyzing behavioral, molecular and metabolic markers. After 10-days of treatment with TUDCA, we observed in our model an improvement in the main neuropathological markers of Alzheimer's, accompanied by an improvement in glucose tolerance and insulin sensitivity, an increase in the total number of beta cells in the pancreatic islets and an increase in glucose-stimulated insulin secretion, comparing to animals that were treated with PBS. In addition, we also observed lower body weight, adiposity and food intake, higher leptin sensitivity and higher energy expenditure in animals treated with the bile acid. Our results suggest that TUDCA has beneficial effects on the glucose and energetic metabolism of AD mice model, attenuating the metabolic damages observed in this disease. This study corroborates the evidences that Alzheimer's is a disease that affects the central nervous system and the peripheral tissues, and also brings contributions about the understanding of the metabolic and molecular parameters that are altered in AD mice model. (AU)

• FAPESP's process: 18/20213-2 - Role of TUDCA bile acid in the glycemic and energetic metabolism of mice with Alzheimer's and senile
• Grantee: Lucas Zangerolamo
• Support Opportunities: Scholarships in Brazil - Master