Modulação da Expressão da AQUAPORINA-4 Cerebral pelo Hormônio da Tireoide (T3) durante o período de desenvolvimento do Sistema Nervoso Central de Camundongos Swiss

Abstract

Introduction: The thyroid hormones (TH) L-3,5,3 ', 5'-Tetraiodothyronine (Thyroxine/ T4) and L-3,5,3'-Triiodothyronine (T3) are classically known for their roles in homeostasis, cell maturation and differentiation during embryonic development. In astrocytes, T3 regulates extracellular matrix (ECM) proteins expression and secretion of growth factors during brain development. Aquaporins (AQP's) are a family of small integrated membrane proteins that play a crucial role in bidirectional water transport across plasma membranes. AQP4 is the main brain water channel predominantly expressed in the Blood-Brain Barrier (BBB) astrocytes end-feet encircling endothelial cells and has been pointed out as a therapeutic targetin pathological conditions as neuromyelitis optica, astrocytomas, and stroke. Objective: In the present study, we imed to investigate if AQP4 expression during Central Nervous System (CNS) developmentin Swiss mice was on the modulation of T3 thyroid hormone. Method: Females on the 18th day of pregnancy or young males 27 and 57 days old, received intraperitoneally 1µg/g of T3 hormone diluted in 0.02N NaOH solution or vehicle only for three consecutive days. Immunohistochemical assay for AQP4 and GFAP (Glial Fibrillar Acid Protein) were performed to distribution and localization of AQP4 in brain astrocytes. Results: When compared to control group, treatment with T3 (1µg / g) significantly decreased AQP4 expression in the cerebral cortex of newborn P0 animals (p <0.02). During adulthood, however, treatment with T3 increased AQP4 expression (p <0.0001) and showed a slightly no statistically significant higher immunoreactivity than untreated group in 60-day-old animals. Conclusion: The expression of AQP4 varies according to the CNS stage of development and is modulated in different phases by the thyroid hormone T3. Therefore, our findings indicate T3 as a potential modulator of AQP4 expression during different stages of central nervous system development.