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 toxicity of neurons in culture (Cosi et al., 1994). Since injection of the excitatory amino acid, kainic acid (KA) into the rat striatum induces a delayed neuronal death, the effects of this in vivo excitotoxin lesioning procedure on striatal PARP activity was investigated. PARP activity was measured in striatal extracts both in the absence ("endogenous" activity) and presence ("total" activity) of exogenously-added fragmented DNA. KA (5nmols/1microl) produced significant and time-dependent changes in striatal PARP activity, compared to saline-injected control animals: no changes at 6h after intrastriatal KA, a 68% and 48% decrease in endogenous and total PARP activity respectively 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. PARP cleavage was not detected at any time point. These results suggest a participation of PARP in KA-induced toxicity in the brain in vivo.
Cosi
C
C
Division of Neurobiology I, Centre de Recherche Pierre Fabre, Castres, France. cristina.cosi@pierre-fabre.com
Cavalieri
E
E
Carcereri de Prati
A
A
Marien
M
M
Suzuki
H
H
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011065:Poly(ADP-ribose) Polymerases; D007608:Kainic Acid