Effects of circadian oscillation on the role of astrocytes as supplier of active thyroid hormone

• Grant number: 24/02561-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Kil Sun Lee
• Grantee: Leslie Liandra Duarte da Rosa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/12605-8 - Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system, AP.TEM

Abstract

Sleep deprivation is a health problem that affects a huge proportion of Brazilian population, and is related to the development and worsening of many neurodegenerative disorders, such as Alzheimer's diseases, Parkinson's diseases and epilepsy. This relationship emerges from the dysregulation of sleep-wake cycle, which is supposed to be synchronized in every cell of the organism mainly by the melatonin hormone. Its dysregulation causes significant homeostatic changes. Molecularly, sleep deprivation affects many pathways that culminate in accumulation and aggregation of beta amyloid peptides (A²), which fail to fulfill their physiological functions and begin to have harmful functions when they are not correctly cleared. Sleep deprivation also results in hormonal changes, as it occurs with the thyroid hormones, T3 and T4, and its transporters such as MCT8 and OATP1C1. The alterations of thyroid hormones availability affect the expression of ApoE and its receptors LRP1, LRP4 and LDL-R, important proteins to clearance of beta-amyloid peptides. In the central nervous system (CNS), astrocytes participate in the uptake of T4 (inactive) next to the blood-brain barrier and convert T4 into T3 (active). Based on this information, the present project aims to evaluate the profile of expression of the proteins involved in the thyroid hormones homeostasis in astrocytes submitted to a mimetic condition of circadian oscillation and sleep deprivation. The data obtained from this study can help in the understanding of astrocytes behavior as a component of blood-brain barrier and cooperator of neuronal activities.