Basal ganglia lesions in the rat: effects on quinolinic acid metabolism.
Experimental basal ganglia lesions were produced in order to examine the effect of neuronal loss on quinolinic acid (QUIN) metabolism. The latter was investigated by measuring the activities of QUIN's biosynthetic enzyme, 3-hydroxyanthranilic acid oxygenase (3-HAO) and its degradative enzyme, quinolinic acid phosphoribosyltransferase (QPRT). Striatal ibotenic acid lesions caused a steady increase in striatal QPRT activity, reaching 280% of control levels 21 days after the lesion. In the same tissue, 3-HAO activity, too, was elevated. It rose to 436% of control after 7 days and to a lesser degree (+309%) after 3 weeks. Immunotitration experiments using anti-rat 3-HAO antibodies and kinetic analysis of lesioned and control striata showed that the increase in 3-HAO was due to de novo production of enzyme protein. The large increases in striatal enzyme activities after 7 days were accompanied by smaller increases in both 3-HAO and QPRT activities in the ipsilateral substantia nigra. Physical destruction of corticostriatal glutamatergic fibers resulted in increases in striatal 3-HAO (+216%) and QPRT (+243%) activities after one week. No changes in nigral or striatal QUIN metabolism were recorded 7 days after an intranigral injection of 6-hydroxydopamine. These data confirm the notion of a largely glial localization of the QUIN system in the basal ganglia, and correlate well with recent observations in brain tissue from Huntington's disease victims.
Schwarcz
R
R
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.
Okuno
E
E
White
R J
RJ
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006892:Hydroxydopamines; D007051:Ibotenic Acid; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D009498:Neurotoxins; D016627:Oxidopamine; D010430:Pentosyltransferases / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D006892:Hydroxydopamines; D009498:Neurotoxins; D011725:Pyridines; D011805:Quinolinic Acids; D015095:3-Hydroxyanthranilic Acid; D007051:Ibotenic Acid; D016627:Oxidopamine; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017378:Quinolinic Acid