EXCITOTOXIC LESIONS OF THE RAT STRIATUM - DIFFERENT RESPONSES OF KYNURENINE PATHWAY ENZYMES DURING ONTOGENY

Excitotoxic lesions of the adult rat striatum result in reactive glios is and an associated increase in the activities of the astrocytic enzy mes 3-hydroxyanthranilic acid oxygenase (3HAO) and kynurenine aminotra nsferase (KAT), which are responsible for the biosynthesis of the neur otoxin quinolinic acid and the neuroprotectant kynurenic acid, respect ively. Unilateral ibotenate injections were made in the striatum of 7- , 14-, 21- and 28-day- and 2.5-month-old rats to study the reaction of 3HAO and KAT when injury is inflicted during ontogeny. By one week, a ll lesioned striata showed a > 50% decrease in the activity of the neu ronal marker enzyme glutamic acid decarboxylase. At this timepoint, le sion-induced elevations in 3HAO activity increased progressively from 130 to 206, 280, 385 and 456% of the contralateral striatum in the fiv e age groups studied. In contrast, in the same animals the respective increases in striatal KAT activity were 601, 350, 312, 259 and 159% (1 2 = 6-13 per group). In all age groups, statistically significant lesi on-induced increases in 3HAO and KAT were seen up to 4 weeks after the ibotenate injection. Rats receiving an intrastriatal injection of ibo tenate on postnatal day 7 also showed an increase in the striatal tiss ue level of kynurenic acid 1 week after the lesion. These data demonst rate that substantial qualitative differences exist between the immatu re and adult rat in the reaction of two glial enzymes to striatal inju ry. Moreover, the ability of the immature brain to mobilize kynurenic acid production preferentially may play a role in the brain's response to perinatal injury.