Upregulation of the aromatic amino acid decarboxylase under neonatal asphyxia

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to asphyxia. However, the respective enzyme activities have not yet been measured in the living neonatal brain. In this study, we have used 18F-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron-emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine (DA), in the brain of newborn piglets. Simultaneously, the cerebral blood flow (CBF) was measured with colored microspheres. Asphyxia elicited an up to threefold increase of the CBF. Despite this, the blood-brain transfer of FDOPA as well as the clearance rate constants from brain were unchanged. However, the synthesis rate of FDA from FDOPA was significantly increased in frontal cortex, striatum, and midbrain. This increase of the AADC activity and the decrease of monoamine oxidase activity may contribute to the increase of extracellular DA during asphyxia which is expected to be involved in severe disturbances of neuronal metabolism, e.g., by generating free radicals.