No abstract

We have previously shown that thyroid hormone (T 3 ) regulates mitochondrial gene expression, morphology and transmembrane potential in the developing brain. Here, we have analysed the effect of thyroid hormone on mitochondrial function in different brain regions. For this purpose we have determined, in control, hypothyroid and T 3 -treated hypothyroid neonatal rats, the rate of oxidative phosphorylation in isolated mitochondria and the activity of the respiratory complexes in tissue homogenates. Our results showed a decrease in oxidative phosphorylation rate (only in the presence of NADH-generating substrates) and mitochondrial complexes I and III activity in the cerebral cortex and striatum of hypothyroid neonates, but not in the other areas analysed (hippocampus, cerebellum, thalamus, mid brain and brain stem). In parallel with mitochondrial activity, the levels of mitochondrially encoded transcripts were decreased only in the cerebral cortex and striatum of hypothyroid rats. The administration of T 3 corrected all these parameters. In summary, this study showed a down-regulation of mitochondrial gene expression accompanied by a decrease in mitochondrial activity in the cerebral cortex and striatum of developing hypothyroid neonatal rats.

The prostaglandin J 2 derivative 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) is a very active compound with important effects on inflammation, apoptosis, and cell growth processes. To exert this broad range of effects, 15d-PGJ 2 binds and alters the activity of diverse proteins, which consequently are postulated to be mediators of its action. Among them are the transcription factors peroxisome proliferator-activated receptor ␥ and nuclear factor B, which are thought to play an essential role in the antitumorigenic and anti-inflammatory actions of 15d-PGJ 2 . Here, we show that 15d-PGJ 2 , at micromolar concentrations, efficiently blocks state 3 oxygen consumption in intact nonsynaptic mitochondria isolated from rat cerebral cortex. This effect is attributable to the inhibition by this prostaglandin of the activity of the enzyme NADH-ubiquinone reductase (complex I) of the mitochondrial respiratory chain. In addition to this, 15d-PGJ 2 dramatically increases the rate of reactive oxygen species generation by complex I. The inhibition by 15d-PGJ 2 of complex I activity was abolished by dithiothreitol, which raises the possibility that adduct formation with a critical component of complex I accounts for the inhibitory effect of this prostaglandin. These results clearly identified mitochondrial complex I as a new target for 15d-PGJ 2 actions. -Martínez, B., A. Pérez-Castillo, and A. Santos. The mitochondrial respiratory complex I is a target for 15-deoxy-⌬ 12,14 -prostaglandin J 2 action. J. Lipid Res. 2005. 46: 736-743.

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.

Notifiable avian influenza (NAI) had never been reported in Spain, until July 2006 when a dead Great Crested Grebe (Podiceps cristatus) was found positive to the highly pathogenic H5N1 subtype as part of the active wild bird surveillance plan. The current program of the Spanish Ministry of Agriculture, Fisheries, and Food (MAPA)'s strategic preventive plan against NAI is divided in the following parts: identification of risk areas and risk wild bird species, increased biosecurity measures, early detection of infection with surveillance intensification and development of rapid diagnostic tests, and other policies, which include continuing education and training to ensure early detection of the disease. In 2003 an active surveillance plan was introduced for domestic fowl; the plan was extended to wild birds in 2004. A total of 18,780 samples in poultry and 3687 samples in wild birds had been analyzed through December 2005 to detect the presence and spread of avian influenza subtypes H5 and H7. In the present work we suggest some contributions to be implemented in MAPA's action plan: 1) the identification of risks because of migratory birds, within the risk assessment of the introduction of NAI virus in Spain and 2) an interactive digital simulator of the disease developed for continuing education and training.