Neuronal Mitochondrial Morphology and Transmembrane Potential Are Severely Altered by Hypothyroidism during Rat Brain Development.

We recently demonstrated that thyroid hormone is an important regulator of mitochondrial gene expression during brain development. To gain further insights into the consequences of this regulation, we have performed functional and structural analysis of brain mitochondria from control and hypothyroid neonatal rats. Flow cytometric analysis showed a significant decrease in the mitochondrial transmembrane potential in hypothyroid animals compared with controls, which was reversed after 48 h, but not after 2 h, of thyroid hormone administration, suggesting that the functional alterations observed are the consequence of changes in mitochondrial gene expression. In addition, band shift studies showed a protein bound to the rat mitochondrial promoter differentially regulated by thyroid state. Electron microscopic analysis of cerebral cortex, striatum, and hippocampus revealed marked differences in the morphology of neuronal mitochondria from control and hypothyroid neonates. Hypothyroid mitochondria presented a decrease in the area of the inner membrane plus cristae in all areas studied, except for the hippocampal CA1 neurons and nonneuronal cell types. The observations reported here provide a basis for the known biochemical action of thyroid hormone on brain development.