Dramatic brain aminergic deficit in a genetic mouse model of phenylketonuria

Clinical data suggest that brain catecholamines and serotonin are deficient in phenylketonuria (PKU), an inherited metabolic disorder that causes seve re mental retardation and neurological disturbances. To test this hypothesi s, brain tissue levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryp tamine (5-HT) and their metabolites were evaluated in the genetic mouse mod el of PKU (Pah(enu2)). Results indicated a significant reduction of 5-HT le vels and metabolism in prefrontal cortex (pFC), cingulate cortex (Cg), nucl eus accumbens (NAc), caudate putamen (CP), hippocampus (HIP) and amygdala ( AMY). NE content and metabolism were reduced in pFC, Cg, AMY and HIP. Final ly, significantly reduced DA content and metabolism was observed in pFC, NA c, CP and AMY. In pFC, NAc and CP there was also a marked reduction of DA r elease. NeuroReport 11:1361-1364 (C) 2000 Lippincott Williams & Wilkins.