Repercussions of triiodothyronine (T3) association to insulin treatment on insulin signaling and expression of degeneration and survival markers in central nervous system (CNS) of diabetic rats

• Grant number: 19/18377-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): August 01, 2020
• Effective date (End): December 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Talles Moraes de Sousa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Nowadays, Diabetes Mellitus (DM) is considered the most prevalent endocrinopathy worldwide. It has been demonstrated that changes in glucose metabolism and insulin deficiency and/or resistance in central nervous system (CNS) are related to neurodegenerative diseases. It is known that the induction of DM1 leads to hypothyroidism, and that thyroid hormones (TH), besides being essential for neurodevelopment, are important regulators of glucose metabolism and insulin signaling in tissues. In this sense, studies from our laboratory indicated that DM rats treated with triiodothyronine (T3) show improvement of CNS insulin signaling. Moreover, it was demonstrated that the association of T3 (1.5 µg/100g) with half of the replacement insulin dose (3U) promotes greater benefits in glycemic homeostasis when compared to the standard treatment (insulin 6U); however, the repercussions of this treatment in the CNS have not been explored yet. This study aims to investigate the effects of this association on the expression of proteins involved in insulin signaling pathway and preservation and plasticity of the CNS of adult DM rats. To this end, Wistar rats (~250 g) will be used and part of them will be induced to DM by alloxane injection, while the others will receive the vehicle (non DM group). Part of the DM animals will be treated with T3 and insulin (in the doses mentioned above), or with 6U of insulin (replacement dose) or saline (0,9%) solution (DM control group) for 4 weeks. Afterwards, the animals will be anesthetized and euthanized for analyses of the expression of proteins related to insulin signaling, BDNF and neurodegeneration markers in cerebral cortex and hippocampus, by Western Blotting and ELISA. Additionally, the morphological analysis of these brain areas will be done to mark apoptosis using Fluoro-Jade C, as well as the quantification of synapses using anti-MAP2 antibodies (neural filaments), anti-synapsin 1 (pre-synaptic protein) and anti-Homer 1 (postsynaptic protein), to assess neuronal plasticity. (AU)