NEURONAL MITOCHONDRIAL MORPHOLOGY AND TRANSMEMBRANE POTENTIAL ARE SEVERELY ALTERED BY HYPOTHYROIDISM DURING RAT-BRAIN DEVELOPMENT

We recently demonstrated that thyroid hormone is an important regulato r of mitochondrial gene expression during brain development. To gain f urther insights into the consequences of this regulation, we have perf ormed functional and structural analysis of brain mitochondria from co ntrol 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 4 8 h, but not after 2 h, of thyroid hormone administration, suggesting that the functional alterations observed are the consequence of change s in mitochondrial gene expression. In addition, band shift studies sh owed 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 m orphology of neuronal mitochondria from control and hypothyroid neonat es. Hypothyroid mitochondria presented a decrease in the area of the i nner membrane plus cristae in all areas studied, except for the hippoc ampal CA1 neurons and nonneuronal cell types. The observations reporte d here provide a basis for the known biochemical action of thyroid hor mone on brain development.