Effects of a co-treatment with pyruvate and creatine on dendritic spines in rat hippocampus and posterodorsal medial amygdala in a phenylketonuria animal model

Phenylketonuria (PKU) is the most frequent aminoacidopathy that damage the central nervous system and is characterized by neural injury, mental retardation and accumulation of phenylalanine and its metabolites in plasma and tissues. So far, the only effective protection against brain injury is the administration of special phenylalanine-free diets. Animals with lesions in the hippocampus and amygdala had behavioral impairments indicating the importance of the integrity of these brain structures in learning and memory tasks which are disability characteristics of patients affected by PKU. In the present study we aimed to test the effect of the combination of two energetic and antioxidant compounds–pyruvate and creatine (intraperitoneal injections of 0.2 mg/g of body weight and 0.4 mg/g of body weight, respectively, treatment from the 7th to the 28th postnatal day)–in animals subjected to a chronic model of PKU. To assess likely effects, the density of dendritic spines in the hippocampal CA1 region and in the posterodorsal medial amygdala of 60-day-old male rats were analyzed under confocal microscopy. Present results showed that the co-treatment with pyruvate and creatine prevented the reduction in dendritic spine density in the stratum radiatum of the CA1 hippocampal field and in the posterodorsal medial amygdala of PKU animals. If this can also occur in PKU patients, it is possible that creatine and pyruvate may help to prevent brain damage in patients under specific diet.