Glial glutamate dehydrogenase: ultrastructural localization and regional distribution in relation to the mitochondrial enzyme, cytochrome oxidase.
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.
Aoki
C
C
Department of Neurology, Cornell University Medical College, New York, NY 10021.
Milner
T A
TA
Berger
S B
SB
Sheu
K F
KF
Blass
J P
JP
Pickel
V M
VM
D000818:Animals; D001921:Brain / Q000201:enzymology*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006651:Histocytochemistry; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology*; D009457:Neuroglia / Q000201:enzymology*; D051381:Rats; D014018:Tissue Distribution
D005969:Glutamate Dehydrogenase; D003576:Electron Transport Complex IV