Hypothyroidism decreases the biogenesis in free mitochondria and neuronal oxygen consumption in the cerebral cortex of developing rats.
Thyroid hormone plays a critical role in mitochondrial biogenesis in two areas of the developing brain, the cerebral cortex and the striatum. Here we analyzed, in the cerebral cortex of neonatal rats, the effect of hypothyroidism on the biogenesis in free and synaptosomal mitochondria by analyzing, in isolated mitochondria, the activity of respiratory complex I, oxidative phosphorylation, oxygen consumption, and the expression of mitochondrial genome. In addition, we studied the effect of thyroid hormone in oxygen consumption in vivo by determining metabolic flow through (13)C nuclear magnetic resonance spectroscopy. Our results clearly show that in vivo, hypothyroidism markedly reduces oxygen consumption in the neural population of the cerebral cortex. This effect correlates with decreased free mitochondria biogenesis. In contrast, no effect was observed in the biogenesis in synaptosomal mitochondria. The parameters analyzed were markedly improved after T(3) administration. These results suggest that a reduced biogenesis and the subsequent reduction of respiratory capacity in free mitochondria could be the underlying cause of decreased oxygen consumption in the neurons of the cerebral cortex of hypothyroid neonates.
Martinez
Bienvenida
B
Departamentos de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Rodrigues
Tiago B
TB
Gine
Elena
E
Kaninda
John P
JP
Perez-Castillo
Ana
A
Santos
Angel
A
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003409:Congenital Hypothyroidism / Q000503:physiopathology; D005260:Female; D007037:Hypothyroidism / Q000139:chemically induced / Q000503:physiopathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D024101:Mitochondrial Proteins; D008713:Methimazole