SELECTIVE DISTRIBUTION OF LACTATE-DEHYDROGENASE ISOENZYMES IN NEURONSAND ASTROCYTES OF HUMAN BRAIN

In vertebrates, the interconversion of lactate and pyruvate is catalyz ed by the enzyme lactate dehydrogenase. Two distinct subunits combine to form the five tetrameric isoenzymes of lactate dehydrogenase. The L DH-5 subunit (muscle type) has higher maximal velocity (V-max) and is present in glycolytic tissues, favoring the formation of lactate from pyruvate. The LDH-1 subunit (heart type) is inhibited by pyruvate and therefore preferentially drives the reaction toward the production of pyruvate. There is mounting evidence indicating that during activation the brain resorts to the transient glycolytic processing of glucose. Indeed, transient lactate formation during physiological stimulation h as been shown by H-1-magnetic resonance spectroscopy. However, since w hole-brain arteriovenous studies under basal conditions indicate a vir tually complete oxidation of glucose, the vast proportion of the lacta te transiently formed during activation is likely to be oxidized. Thes e in vivo data suggest that lactate may be formed in certain cells and oxidized in others. We therefore set out to determine whether the two isoforms of lactate dehydrogenase are localized to selective cell typ es in the human brain. We report here the production and characterizat ion of two rat antisera, specific for the LDH-5 and LDH-1 subunits of lactate dehydrogenase, respectively. Immunohistochemical, immunodot, a nd western-blot analyses show that these antisera specifically recogni ze their homologous antigens. Immunohistochemistry on 10 control cases demonstrated a differential cellular distribution between both subuni ts in the hippocampus and occipital cortex: neurons are exclusively st ained with the anti-LDH1 subunit while astrocytes are stained by both antibodies. These observations support the notion of a regulated lacta te flux between astrocytes and neurons.