Caracterisation of the action of triiodothyronine (T3) and the thyromimetic sobetiramide (Sob-AM2) in the hippocampal formation of Wistar rats with Diabetes induced by alloxan

• Grant number: 22/12190-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2023
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Johnatas Maldonado Campos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is an endocrinopathy that occurs due to impairments in the secretion/action of insulin, which is mainly characterised by hyperglycaemia. In the central nervous system (CNS), insulin deficiency impairs several processes, like the cognitive ones, which are related to the hippocampal formation (HF). DM is also associated to inflammation and thyroid disfunctions, mainly hypothyroidism, where cognitive impairments are reported. Thyroid hormones (THs) increase glucose uptake, utilisation and hepatic glucose production; besides, it activates enzymes that participate in the insulin signalling (IS) pathway. We demonstrated that alloxan-induced DM in rats causes hypothyroidism and that T3 treatment reduces glycaemia, TSH levels, inflammatory cytokines expression and insulin resistance, improving the IS in its target tissues and in the CNS. Later studies associating T3 to 3 units (3U) of insulin in the same experimental model demonstrated better results and serum TSH recovery to control group levels. This project aims to evaluate the effects of T3 treatment, associated or not to insulin (3U), on the IS and inflammation in the HF of DM rats induced by alloxan. Considering evidences that, at least part of the actions of the THs in the hippocampus depends of the interaction of T3 with the beta isoform of its receptor (THR²), we also intend to evaluate in this experimental model the effects of the treatment with sobetiramide (Sob-AM2), a THR² specific agonist which action is potentiated in the CNS. If Sob-AM2 reproduces the T3 effects, we'll identify THR² isoform as the one involved in these effects. We will also evaluate the cognitive function of these animals through behavioural tests, and whether insulin associated to T3, and/or Sob-AM2, promotes any other positive effects in these parameters. (AU)