Rat PKU Model Display Gender-Based Neuroinflammatory Changes: Proinflamatuary Cytokines and Lipid Peroxidation

Abstract

Phenylketonuria (PKU) results from congenital defects of amino acid metabolism. Accumulated phenylalanine crosses the blood-brain barrier and causes permanent brain damage, but the neuro-pathophysiology underlying phenylketonuria is not fully understood. Chemically-induced rat phenylketonuria model of both genders was generated to examine the role of inflammatory response, lipid peroxidation and oxidative stress in the prefrontal cortex. Our results showed that in phenylketonuria there was an increase in lipid peroxidation compared to controls, which was significantly different only in males (p<0.001). In male rat PKU groups, statistically significant differences were also observed in serum tryptophan (p<0.001) and interleukin-1β levels (p=0.014) as compared to male controls. In this study, gender-based changes in neuroinflammation and lipid peroxidation were reported for the first time in a PKU model.