Thyroid hormone signaling in hippocampus of obese rats

• Grant number: 15/13235-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2015
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Miriam Oliveira Ribeiro
• Grantee: Miriam Oliveira Ribeiro
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Presbiteriana Mackenzie (UPM). Instituto Presbiteriano Mackenzie. São Paulo , SP, Brazil
• Associated research grant(s): 16/50447-0 - Role of type 3 deiodinase (D3) in depression induced by social isolation, AP.R SPRINT

Abstract

T3 is key in the development and maintenance of the central nervous system (CNS) by modulating the expression of proteins related to neuronal plasticity, such as BDNF, NT -3, NGF, known as neurotrophins . In hypothyroid animals there is a significant reduction of these proteins and decreased hippocampal neurogenesis resulting in behavioral changes such as depression and impaired memory consolidation. Thyroid hormone is secreted in the form of T4 and converted into T3, the physiologically active form of thyroid hormone, throughthe deiodinases activity. The deiodinases are responsible for the regulation or the amount of T3 available to the brain. They are activate T4 to T3, process catalyzed by D2, or inactivate the T4 to rT3, the D3 action. Obesity is also related to similar changes observed in hypothyroidism, i.e. decrease in neurotrophin synthesis in the hippocampus, depression and loss of memory. Thus, our working hypothesis is based on the possibility that in obesity there is a decrease in T3 signaling in the brain and the local hypothyroidism would be the basis for behavioral changes observed in these individuals. To test our hypothesis, we will study Wistar rats treated with high-fat diet (40%) and once the obesity is estabilished, assess depressive behavior and learning ability and memory formation through behavioral tests. Later we will analyze the expression of D3 enzyme by immunohistochemistry, gene expression of D2 and D3 as well as the expression of genes regulated by T3 in the brain by PCR real time (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)

NASCIMENTO, BRUNA P. P.; BOCCO, BARBARA M. L. C.; FERNANDES, GUSTAVO W.; FONSECA, TATIANA L.; MCANINCH, ELIZABETH A.; CARDOSO, CAROLINA V.; BONDAN, EDUARDO F.; NASSIF, RENATA J.; CYSNEIROS, ROBERTA M.; BIANCO, ANTONIO C.; et al. Induction of Type 2 Iodothyronine Deiodinase After Status Epilepticus Modifies Hippocampal Gene Expression in Male Mice. Endocrinology, v. 159, n. 8, p. 3090-3104, AUG 2018. (13/09133-3, 15/13235-1)

FERNANDA B. LORENA; BRUNA P. P DO NASCIMENTO; ESTHER L. R. A. CAMARGO; MARIA M. BERNARDI; ANDRÉ R. FUKUSHIMA; JULIA DO N. PANIZZA; PAULA DE B. NOGUEIRA; MARLLOS E. S. BRANDÃO; MIRIAM O. RIBEIRO. Long-term obesity is associated with depression and neuroinflammation. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 65, n. 5, p. 537-548, 2021-11-12. (15/13235-1, 14/15556-7)