Thyroid Hormone Insufficiency Alters the Pattern of Expression of the Ca2+-Binding Proteins in the Rat Neonatal Cortex

Thyroid hormones (TH) are critical for brain development. Parvalbumin (Pvalb) and calbindin (Calb) are Ca2+-binding proteins expressed in GABAergic interneurons. In rats, a phenotypic switch from Calb+- to Pvalb+- expression occurs in interneurons around postnatal day (PN) 10. Developmental TH insufficiency reduces Pvalb+ cell number, GABAergic cell number remaining constant, suggesting a TH-dependent delay in the transition from Calb+ to Pvalb+ expression. This question was addressed in two studies: 1) Pregnant rats were administered the TH-synthesis inhibitor, propylthiouracil (PTU) via drinking water ( 0 & 3ppm) from gestational day 6 to postnatal day (PN) 14. Brains of PN14 offspring were immersion-fixed and prepared for immunohistochemistry.  2) The second study expanded this inquiry to a dose response analysis and included examination of a third class of inhibitory neurons expressing another calcium binding protein known as calretinin

Impact/Purpose

Thyroid hormones (TH) are critical for brain development. Parvalbumin (Pvalb) and calbindin (Calb) are Ca2+-binding proteins expressed in GABAergic interneurons. In rats, a phenotypic switch from Calb+- to Pvalb+- expression occurs in interneurons around postnatal day (PN) 10.  TH-dependent interference with the development of interneurons can have significant deleterious effects on maturation of neural circuitry in the developing brain. 

Citation

Hawks, M., J. Ford, Ryno Thomas, C. Wood, AND M. Gilbert. Thyroid Hormone Insufficiency Alters the Pattern of Expression of the Ca2+-Binding Proteins in the Rat Neonatal Cortex. U.S. Environmental Protection Agency, Washington, DC, 2025. [DOI: 10.23719/d-zpd6]

DOI: Thyroid Hormone Insufficiency Alters the Pattern of Expression of the Ca2+-Binding Proteins in the Rat Neonatal Cortex