Development of behavioural dysfunctions in accelerated-senescence OXYS rats is associated with early postnatal alterations in brain phosphate metabolism

Abstract

We recently demonstrated that senescence-accelerated OXYS rats may represent a model adequate for studying aging processes. The animals of this strain have a particularly short life span; they display early cataract, macular dystrophy, hypertension, and changes in cognitive and emotional spheres. Mitochondrial dysfunctions have been suggested to be a causal factor for the accelerated senescence in these animals. In the present study we investigated whether behavioral alterations in OXYS rats could be associated with changes in high-energy phosphate and phospholipid metabolism of the brain in the early postnatal period. The development of behavioral dysfunction in OXYS rats relative to Wistar was investigated by measuring locomotor exploratory activity and the degree of anxiety at 4 and 12 weeks of age in open-field and elevated plus maze tests, respectively. Brain energy metabolism was evaluated at 2, 3, 4 and 12 weeks of age by calculating the ratios of PCr/Pi, PCr/ATP and phosphate potential (ATP/ADP×Pi) measured by 31P NMR spectroscopy. We found that the behavioral alterations in OXYS rats, i.e. the increased anxiety and the decreased exploratory activity, were not congenital but developed during the period from 4 to 12 weeks of age. The study of high-energy phosphates has not revealed any signs of energy deficiency in OXYS rat's brain but indicated changes in PCr metabolism at 2 and 3 weeks of age when compared with Wistar rats. Furthermore, alterations in phospholipids turnover were also found in young OXYS rats. The data suggest that the changes in phosphate metabolism may have impacts on the development of behavioral deficits in OXYS rats.