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. https://doi.org/10.23719/d-zpd6

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. 

Description:

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

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