Role of TUDCA bile acid in the glycemic and energetic metabolism of mice with Alzheimer's and senile

• Grant number: 18/20213-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2019
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helena Cristina de Lima Barbosa
• Grantee: Lucas Zangerolamo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Alzheimer's is a neurodegenerative disease caused by the accumulation and extracellular deposition of the amyloid beta protein in the hippocampus. This process results in neuronal death, leading to memory impairment and progressive cognitive decline. Aging is the main risk factor for the development of Alzheimer's, and the hippocampus is severely affected in this condition. Recent studies show that insulin resistance in the nervous system, reduced glucose utilization and deficiencies in energy metabolism are often found in Alzheimer's and elderly individuals. In this context, tauroursodeoxycholic bile acid (TUDCA) has been used in neurodegenerative disease models, because it has antiapoptotic properties, besides acting in metabolic pathways, modulating insulin secretion and signaling, as well as endoplasmic reticulum stress. In Alzheimer's disease, TUDCA treatment reduces the accumulation of amyloid beta plaques in APP/PS1 transgenic mice, attenuating the damage caused by this disease, through a mechanism not yet fully elucidated. In this work, using C57BL/6 mice that will receive intracerebroventricular injection of streptozotocin for induction of Alzheimer's, as well as senile mice, both treated with 300 mg/kg of intraperitoneal TUDCA, we aimed to evaluate the role of this bile acid in the glycemic and energetic metabolism of these experimental models, analyzing behavioral, molecular and metabolic markers characteristic of the disease. This project will contribute to understanding the metabolic and molecular parameters that are altered in mice with Alzheimer's and senile, as well as potential elucidation of the signaling pathways in which the bile acid TUDCA participates, seeking possible preventive methods and treatments for Alzheimer's and cognitive impairment due to aging.

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZANGEROLAMO, L.; VETTORAZZI, J. F.; SOLON, C.; ENGEL, D. F.; SOARES, G. M.; VELLOSO, L. A.; CARNEIRO, E. M.; BOSCHERO, A. C.; BARBOSA, H. C. L.. Alzheimer's disease impacts the hypothalamus and induces energetic homeostasis deregulation in mice. Diabetologia, v. 63, n. SUPPL 1, p. 2-pg., 2020-09-01. (18/20213-2, 15/23729-1)

ZANGEROLAMO, L.; VETTORAZZI, J. F.; SOLON, C.; SOARES, G. M.; VELLOSO, L. A.; CARNEIRO, E. M.; BOSCHERO, A. C.; BARBOSA-SAMPAIO, H. C. L.. Effects of the bile acid TUDCA on glucose metabolism of mice with Alzheimer's disease. Diabetologia, v. 62, p. 1-pg., 2019-09-01. (18/20213-2, 15/23729-1)

ZANGEROLAMO, LUCAS; VETTORAZZI, JEAN F.; ROSA, LUCAS R. O.; CARNEIRO, EVERARDO M.; BARBOSA, HELENA C. L.. The bile acid TUDCA and neurodegenerative disorders: An overview. Life Sciences, v. 272, MAY 1 2021. (13/07607-8, 18/06363-1, 15/23729-1, 18/20213-2, 15/12611-0)

ZANGEROLAMO, LUCAS; SOLON, CARINA; SOARES, GABRIELA M.; ENGEL, DAIANE F.; VELLOSO, LICIO A.; BOSCHERO, ANTONIO C.; CARNEIRO, EVERARDO M.; BARBOSA, HELENA CRISTINA L.. Energy homeostasis deregulation is attenuated by TUDCA treatment in streptozotocin-induced Alzheimer's disease mice model. SCIENTIFIC REPORTS, v. 11, n. 1, SEP 13 2021. (13/07607-8, 18/20213-2, 18/06363-1)

ZANGEROLAMO, LUCAS; VETTORAZZI, JEAN F.; SOLON, CARINA; BRONCZEK, GABRIELA A.; ENGEL, DAIANE F.; KURAUTI, MIRIAN A.; SOARES, GABRIELA M.; RODRIGUES, KARINA S.; VELLOSO, LICIO A.; BOSCHERO, ANTONIO C.; et al. The bile acid TUDCA improves glucose metabolism in streptozotocin-induced Alzheimer's disease mice model. Molecular and Cellular Endocrinology, v. 521, FEB 5 2021. (13/07607-8, 15/12611-0, 17/13410-3, 15/23729-1, 18/06363-1, 18/20213-2)

ZANGEROLAMO, LUCAS; CARVALHO, MARINA; BARSSOTTI, LETICIA; SOARES, GABRIELA M.; MARMENTINI, CARINE; BOSCHERO, ANTONIO C.; BARBOSA, HELENA CRISTINA L.. The bile acid TUDCA reduces age-related hyperinsulinemia in mice. SCIENTIFIC REPORTS, v. 12, n. 1, p. 16-pg., 2022-12-23. (18/20213-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ZANGEROLAMO, Lucas. Role of bile acid TUDCA in the glucose and energy metabolism of experimental Alzheimer's disease mice model. 2021. 104 f. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.