Factors involved in the age-related alteration in the efficiency of the brain bioenergetics

Abstract

The synaptic energy state may be defined by the redox state of the intramitochondrial NAD-couple (ΔG ox-red) and the phosphorylation state of adenine nucleotide system (ΔG ATP). The biological energy ‘lost’ by the system during the coupled reactions is calculated as ΔΔG = ΔG ox- red - ΔG ATP . These evaluations are performed in synaptosomes isolated from the forebrain of rats of different ages (20, 60 and 100 weeks of age) and incubated in Krebs-Henseleit-Hepes (pH 7.4) buffer, for 10 min at 24°C. The animals are submitted for 10 min to different degrees of in vivo hypoxia. To better elucidate the mechanism of action, the effects of the pretreatment with agents inducing vasodilation (papaverine), or acting on cerebral carbohydrate metabolism (hopanthenate), or on neurotransmission and cerebral metabolism (theniloxazine) are tested. In synaptosommes isolated from the forebrain of animals submitted to moderate degree of hypoxia ( Pao 2 = 32−29 mmHg) the efficiency of the system is quite similar to that observed in normoxia, with the exception of the older rats. In synaptosomes isolated from the forebrain of rats submitted to severe degree of hypoxia ( Pao 2 = 20−18 mmHg) the efficiency is altered as a function of both aging and severity of hypoxemia. Drug pretreatment may partially interfere with the ΔΔG by hypoxemia, the action being related to the rat age and hypoxic degree. The age-related decrease in the efficiency of the coupled states seems to be related to alteration in the phosphorylation state of adenine nucleotides.