Distribution of the alpha-ketoglutarate dehydrogenase complex in rat brain

The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a key enzyme in mitochondrial oxidation that appears critical to neurodegenerative diseases. Its activity in the brain declines in thiamine-deficient animals, Alzheimer's disease, and Wernicke-Korsakoff syndrome. Since selective cell populations are affected in these disorders, understanding the cellular distribution of KGDHC is important in order to define its role in the pathophysiology of these diseases. We used antisera against both bovine KGDHC and its E1k component to determine the immunocytochemical distribution of the enzyme and compare it with that of another mitochondrial enzyme, pyruvate dehydrogenase complex (PDHC) and a cholinergic neuronal marker, choline acetyltransferase (ChAT) in rat brain. Although low levels of immunoreactivity occurred in neurons, glia, and neuropil throughout the brain, some regions displayed relatively high perikaryal KGDHC enrichment. In the cerebral cortex, high immunoreactivity occurred mostly in layers III, V, and VI. The hippocampal pyramidal layer in CA1 and CA2 exhibited more intense staining than CA3. In the mammillary body, intensely labeled cells occurred in the supramammillary and lateral nuclei, while moderately stained cells predominated in the medial nucleus. The basal forebrain, basal ganglia, reticular and midline thalamic nuclei, red nucleus, pons, cranial nerve nuclei, inferior and superior colliculi, and cerebellar nuclei also contained highly immunoreactive neurons. The distribution of KGDHC overlapped with that of PDHC and colocalized to a limited extent with ChAT. These data are the first to demonstrate KGDHC immunoreactivity in discrete areas of rat brain and are vital to our understanding of selective vulnerability to metabolic insults and disease.