Experimental models of aging and quinolinic acid

Abstract

The normal aging process results in many functional deficits in which the central nervous system (CNS) plays a primary role. However, the study of brain aging involves numerous difficulties, including not only the complex anatomical and functional organization of the brain itself, but also because the length of the experiments themselves and experimental costs are often crucial limitations. This highlights an ever increasing need for the development of alternative model systems capable of mimicking at least to some degree the main alterations observed during the normal aging process. A comparative study of electrophysiological and behavioural features in aged rats and in young rats following chronic administration of a naturally occurring brain metabolite, quinolinic acid (QUIN), recently demonstrated to increase in the cerebral cortex of rats as a function of age, is reported. In rats there occurs an age-dependent increase in the number of animals displaying spontaneous asymptomatic spike-wave discharges, associated with impaired performance in the passive avoidance test. Chronic oral administration of QUIN to young rats also results in cortical spiking activity, without any detectable neuronal cell damage at cortical or hippocampal levels, associated with behavioural deficits similar to those observed in old rats. The utilization of young, QUIN-treated animals may thus perhaps offer an alternative model system for the comprehension of the mechanisms involved in some age-related functional impairments.