Energetic state of aged brain during hypoxia.

Synaptosomes isolated from the forebrain of rats of different ages (20, 60, 100 and 140 weeks of age) and incubated in Krebs-Henseleit-Hepes pH 7.4 buffer (for 10 min at 24 degrees C) were utilized to define the redox state of the intramitochondrial NAD couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The free-energy change (delta delta G) for the coupled reactions was calculated. The animals were subjected for 10 min to different degrees of in vivo hypoxia (52 greater than or equal to PaO2 greater than or equal to 11 mm Hg). In synaptosomes isolated from the forebrain of animals submitted to moderate degrees of hypoxia, the trend of delta delta G was quite similar to that observed in normoxia. In synaptosomes isolated from the forebrain of rats submitted to severe degrees of hypoxia, the delta delta G was markedly altered as function of both aging and severity of hypoxemia. The extensive delta delta G changes were largely supported by alteration of the phosphorylation state of adenine nucleotides. However, in synaptosomes from severely hypoxic rats, aging affected the redox state, too.