Localization of quinolinic acid metabolizing enzymes in the rat brain. immunohistochemical studies using antibodies to 3-hydroxyanthranilic acid oxygenase and quinolinic acid phosphoribosyltransferase

Abstract

Specific antibodies raised in rahhits against 3-hydroxyanthranilic acid oxygenase (EC 1. I.I.I 1.6) and quinolinic acid phosphorihosyltransferasc (F.C 2.4.2.19) were used in immunohistochemical studies to map the cellular localization of the quinolinic acid metabolizing enzymes in the adult male rat brain. 3-Hydroxyanthranilic acid oxygenase immunoreactivity was found to bo present in glial cells of presumed astroglial identity, as judged by co-localization with glial fibrillary acidic protein. 3-Hydroxyanthranilic acid oxygenase-immunoreactive glial cells were present in all brain regions and within major liber tracts. The density of 3-hydroxyanthranilic acid oxygenase-immunoreactive glial cells as well as the intensity of staining of these cells differed among brain regions. In general, telencephalic and diencephalic areas harbored a larger number of 3-hydroxyanthranilic acid oxygenase-positive cells than did mesencephalic regions. In the former regions the caudate nucleus, septum, nucleus accumbens, neocortex and hippocampus were particularly enriched in 3-hydroxyanthranilic acid oxygenase-immunoreactive cells. In the thalamus, regional differences were noted with regard to the intensity of staining among glial cells with high densities of 3-hydroxyanthranilic acid oxygenase cells in the anteroventral, reticular and ventromedial nuclei. In the inferior and superior colliculi, numerous 3-hydroxyanthranilic acid oxygenase-positive glial cells were found in all layers. In the hypothalamus. 3-hydroanthranilic acid oxygenase-immunoreactive glial cells were encountered in the zona incerta. the lateral hypothalamic area, the caudal preoptic region and in the dorsomedial nucleus. In the mesencephalon, the substantial nigra contained numerous, moderately stained cells. At caudal levels of the brain-stem, a relatively large number of cells was detected in the nucleus of the solitary tract, the pontine nucleus and in the fascial nerve nucleus, while other nuclei, such as the reticular formation and the area postrema were relatively poor in 3-hydroxyanthranilic acid oxygenase-immunoreactive cells. In addition to staining of glial cells, neuronal cell bodies containing 3-hydroxyanthranilic acid oxygenase immunoreactivity were detected in the main and in the accessory olfactory bulb, as well as in the ventromedial nucleus of the hypothalamus. Quinolinic acid phosphoribosyltransferase immunoreactivity was observed within glial cells and m association with neuronal cell bodies. Some, but not all, quinolinic acid phosphoribosyltransferase positive glial cells contained glial fibrillary acidic protein (Ko¨hler et al., 1987). In most, but not all. areas the number of quinolinic acid phosphoribosyltransferase positive glial cells was far lower than the number of 3-hydroxyanthranilic acid oxygenase-immunoreactive ones. Numerous quinolinic acid phosphoribosyl-transferase stained glial cells were found in all areas containing 3-hydroxyanthranilic acid oxygenase immunoreactivity. Forebrain regions particularly rich in quinolinic acid phosphoribosyltransferase staining included the olfactory nerve, the medial septum and the diagonal band of Broca. which were found to be particularly rich in quinolinic acid phosphoribosyltransferase-stained glial cells. In the thalamus, the anteroventral, periventricular, ventromedial and reticular nuclei as well as the habenula contained numerous quinolinic acid phosphoribosyltransferase-stained glial cells as did all layers of the inferior and superior colliculli. In the hypothalamus, the lateral preoptic region was rich while the caudal hypothalamic region including the mammillary bodies were relatively poor in quinolinic acid phosphonbosyltransferase-immunoreactive glial cells. Parts of the brain-stem harbored a relatively large number of quinolinic acid phosphoribosyltransferase-immunoreactive cells: the pontine nucleus, the nucleus of the solitary tract, area postrema and the fascial nerve nucleus. Quinolinic acid phosphoribosyltranslerase immunoreactivity was also detected in association with a large number of neurons, scattered throughout the caudate nucleus, the diagonal band of Broca, the substantia innominata. in some hypothalamic nuclei and in most thalamic nuclei. Taken together, these immunohistochemical findings show that cells containing the enzymes immediately responsible for the synthesis and catabolism, respectively, of the excitotoxin quinolinic acid are widely distributed throughout the rat neuraxis. These morphological observations should prove instrumental in guiding further explorations of the cerebral functions of quinolinic acid in health and disease.