Effects of kainic acid lesioning on poly(ADP-ribose) polymerase (PARP) activity in the rat striatum in vivo

Poly(ADP-ribose) polymerase (PARP) is activated in glutamate-induced toxici ty of neurons in culture (Cosi et al., 1994). Since injection of the excita tory amino acid, kainic acid (KA) into the rat striatum induces a delayed n euronal death, the effects of this in vivo excitotoxin lesioning procedure on striatal PARP activity was investigated. PARP activity was measured in s triatal extracts both in the absence ("endogenous" activity) and presence ( "total" activity) of exogenously-added fragmented DNA. KA (5 nmols/1 mu l) produced significant and time-dependent changes in striatal PARP activity, compared to saline-injected control animals: no changes at 6h after intrast riatal KA, a 68% and 48% decrease in endogenous and total PARP activity res pectively at 12h, a doubling in endogenous PARP activity at 24h, and a 382% and 60% increase in endogenous and total activities at 1 week after KA. PA RP cleavage was not detected at any time point. These results suggest a par ticipation of PARP in KA-induced toxicity in the brain in vivo.