INTRASTRIATAL INJECTION OF DOPAMINE RESULTS IN DNA-DAMAGE AND APOPTOSIS IN RATS

OVERFLOW Of the neurotransmitter dopamine (DA) in striatum is implicat ed in the neurodegenerative processes in ischemia, hypoxia and local e xposure to high concentrations of excitatory amino acids. However, how DA causes neurotoxicity is not understood. We report that intrastriat al injection of DA (0.5-1 mu mol/mu l) in Wistar rats produces a robus t increase in apoptotic cell death as determined by both a terminal de oxynucleotidyl transferase catalyzed dUTP-biotin nick labeling (TUNEL) and Klenow polymerase catalyzed [P-32]dCTP labeled DNA ladder. Cells in which apoptosis was induced by DA are characterized by condensed ch romatin, DNA fragmentation, shrinkage and irregular shapes. The apopto tic cell death induced by DA is not due to the effect of hyperosmolar solution since intrastriatal injection of identical concentrations of NaCl on opposite sides of the same rat brains shows little TUNEL-posit ive labeling. The number of apoptotic cells is proportional to the amo unt of DA and length of exposure period. With DA concentrations from 0 to 1 mu mol/mu l, the maximal toxic effect appears at a concentration of 1 mu mol/mu l after 24 h exposure. Demonstration of DA-induced apo ptosis in vivo may provide a potential molecular mechanism for DA neur otoxicity. (C) 1998 Rapid Science Ltd.