Effect of the thyroid hormone receptor beta (TRbeta)-selective thyromimetic GC-1 on brain of 3xTg-AD mice

• Grant number: 17/04491-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2017
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Miriam Oliveira Ribeiro
• Grantee: Bruna Pascarelli Pedrico Do Nascimento
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Presbiteriana Mackenzie (UPM). Instituto Presbiteriano Mackenzie. São Paulo , SP, Brazil

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by gradual loss of memory and deterioration of other cognitive functions. Alzheimer's is the most common form of dementia among older adults. Both thyroid dysfunctions and dementia are conditions that become more prevalent with age and several studies have demonstrated a possible association between these conditions. It is possible that the thyroid hormone (TH) be involved in changes in the processing of amyloid precursor protein (APP), one of the main pathways involved with the onset of AD. However, although the study of therapeutic approaches involving TH be of great relevance, its use brings unwanted side effects such as hypermetabolism and loss of bone and muscle mass, which makes the use of selective analogues of extreme importance. In this regard, recently, the thyroid hormone receptor beta (TRbeta)-selective thyromimetic, GC-1, had its structure modified which resulted in its activation only in the Central Nervous System (CNS). Thus, the aim of the present study is to investigate the effects of GC-1 on the development of neuropathological changes and cognitive function characteristics of AD in 3xTg-AD transgenic mice. For that, we will analyze the cognitive performance of GC-1 treated 3xTg-AD mice through behavioral tests, as well as the presence of senile plaques (SPs), neurofibrillary tangles (NFTs), and neuronal density through histological studies, and the expression of genes related to the neuropathology of AD and related to cognition and memory on brain by RT-qPCR. (AU)

Scientific publications

(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)

BATISTUZZO, ALICE; DE ALMEIDA, GUILHERME G.; BRAS, TAYNA S.; ZUCATO, VICTORIA P.; ARNOLD, ALEXANDRE J. T.; GIANNOCCO, GISELE; SATO, JULIANA M.; YAMANOUCHI, LAIS M.; DIAS, EDUARDO, JR.; LORENA, FERNANDA B.; et al. Multisensory Stimulation Improves Cognition and Behavior in Adult Male Rats Born to LT4-treated Thyroidectomized Dams. Endocrinology, v. 163, n. 9, p. 12-pg., 2022-09-01. (17/04491-0, 17/18277-0)

RAVACHE, THAIS T.; BATISTUZZO, ALICE; NUNES, GABRIELA G.; GOMEZ, THIAGO G. B.; LORENA, FERNANDA B.; DO NASCIMENTO, BRUNA P. P.; BERNARDI, MARIA MARTHA; LIMA, EDUARDA R. R.; MARTINS, DANIEL O.; CAMPOS, ANA CAROLINA P.; et al. Multisensory Stimulation Reverses Memory Impairment in Adr & beta;3KO Male Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 13, p. 17-pg., 2023-07-01. (19/13781-7, 17/18277-0, 17/04491-0)

LORENA, FERNANDA B.; SATO, JULIANA M.; COVIELLO, BEATRIZ MARTIN; ARNOLD, ALEXANDRE J. T.; BATISTUZZO, ALICE; YAMANOUCHI, LAIS M.; DIAS JUNIOR, EDUARDO; DO NASCIMENTO, BRUNA P. P.; FONSECA, TATIANA DE L.; BIANCO, ANTONIO C.; et al. Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism. METABOLITES, v. 12, n. 7, p. 14-pg., 2022-07-01. (17/04491-0, 17/18277-0)