Glial glutamate dehydrogenase: Ultrastructural localization and regional distribution in relation to the mitochondrial enzyme, cytochrome oxidase

Abstract

Glutamate dehydrogenase (GDH) is primarily a mitochondrial enzyme involved in the metabolism of glutamate. We have recently shown by light microscopic immunocytochemistry that, within detergent-permeabilized brain tissue, GDH is enriched in glial cells, particularly in regions utilizing L-glutamate as a neurotransmitter. In this study, we used immunogold labeling to quantitatively establish that the form of the enzyme recognized by the presently used GDH antiserum is associated primarily with a subpopulation of mitochondria in ultrathin, plastic-embedded sections of the rat cortex and striatum. Permeabilization with detergents was omitted in these studies, so as to preserve the ultrastructure. As expected, labeled mitochondria occurred both in neurons and glia. Furthermore, light microscopic comparisons of the regional distributions of peroxidase immunoreactivity for GDH and a histochemical reaction product for a second mitochondrial enzyme, cytochrome oxidase (CO), were used to demonstrate that high levels of GDH in glia of glutamate-receptive areas do not necessarily reflect the areas' demand for elevated oxidative metabolism. While all regions showing intense labeling for glial GDH also exhibited high levels of CO activity, many additional regions showing high levels of CO activity contained no detectable immunoreactivity for glial GDH. These light-microscopic comparisons reveal that the energy requirements are not the only factors accounting for the regional heterogeneity of the enzyme. We conclude that glial mitochondria are heterogeneous with respect to their GDH content and that GDH is enriched in areas exhibiting chronically active glutamatergic transmission.

Regulation of human glutamate dehydrogenases: Implications for glutamate, ammonia and energy metabolism in brain

“…In these tissues, the enzyme is shown to be located in the mitochondria (Hogeboom and Schneider, 1953). Results of more recent ultrastructural investigations using E.M. immunocytochemistry (Aoki et al, 1987;Rothe et al, 1994) are consistent with the mitochondrial localization of GDH.…”

“…Although activity histochemistry (Rothe et al, 1990) and biochemical assays of cultured cells (Patel et al, 1982;Drejer et al, 1985) have shown that GDH is abundant in both neurons and glial cells, immunocytochemical studies (Aoki et al, 1987;Wenthold et al, 1987;Rothe et al, 1990Rothe et al, , 1994 have concluded the enzyme is located predominantly in astrocytes. These investigators observed a rather faint GDH immunoreactivity in certain neuronal populations.…”

“…A considerable regional variation in GDH immunoreactivity has been detected in rat brain (Aoki et al, 1987;Wenthold et al, 1987;Schmitt and Kugler, 1999). Aoki et al (1987) reported that GDH is enriched in regions that receive dense glutamatergic innervation.…”

“…Aoki et al (1987) reported that GDH is enriched in regions that receive dense glutamatergic innervation. In these areas, GDH is found primarily in astrocytic processes surrounding glutamatergic nerve endings (Aoki et al, 1987), thus providing indirect evidence that the enzyme is involved in the metabolism of transmitter glutamate, as previously suggested (Plaitakis et al, 1982).…”

Differential expression of glutamate dehydrogenase in cultured neurons and astrocytes from mouse cerebellum and cerebral cortex

“…Results of those studies showed that GDH immunoreactivity is essentially limited to astrocytes (Aoki et al, 1987;Wenthold et al, 1987;Rothe et al, 1990Rothe et al, , 1994. Moreover, a considerable regional variation in glial GDH immunoreactivity was observed, with the enzyme being particularly enriched in regions that receive dense glutamatergic innervation (Aoki et al, 1987).…”