Excitotoxic lesions of the rat striatum: different responses of kynurenine pathway enzymes during ontogeny.
Excitotoxic lesions of the adult rat striatum result in reactive gliosis and an associated increase in the activities of the astrocytic enzymes 3-hydroxyanthranilic acid oxygenase (3HAO) and kynurenine aminotransferase (KAT), which are responsible for the biosynthesis of the neurotoxin quinolinic acid and the neuroprotectant kynurenic acid, respectively. 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, all lesioned striata showed a > 50 percent decrease in the activity of the neuronal marker enzyme glutamic acid decarboxylase. At this timepoint, lesion-induced elevations in 3HA0 activity increased progressively from 130 to 206, 280, 385 and 456 percent of the contralateral striatum in the five age groups studied. In contrast, in the same animals the respective increases in striatal KAT activity were 601, 350, 312, 259 and 159 percent (n = 6-13 per group). In all age groups, statistically significant lesion-induced increases in 3HA0 and KAT were seen up to 4 weeks after the ibotenate injection. Rats receiving an intrastriatal injection of ibotenate on postnatal day 7 also showed an increase in the striatal tissue level of kynurenic acid 1 week after the lesion. These data demonstrate that substantial qualitative differences exist between the immature and adult rat in the reaction of two glial enzymes to striatal injury. 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.
Ceresoli
G
G
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
Fuller
M S
MS
Schwarcz
R
R
D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D049308:Dioxygenases; D004798:Enzymes / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007051:Ibotenic Acid / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism*; D008190:Lyases; D008297:Male; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000637:Transaminases / Q000378:metabolism
D004798:Enzymes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007051:Ibotenic Acid; D007737:Kynurenine; D010105:Oxygenases; D049308:Dioxygenases; D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; C021481:kynurenine-oxoglutarate transaminase; D008190:Lyases; D005968:Glutamate Decarboxylase; D007736:Kynurenic Acid