The neostriatal mosaic: Compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey ABSTRACTCalcium-binding protein (CaBP) and parvalbumin are two proteins that are expressed in brain and bind calcium in the micromolar range. The immunohistochemical distribution of these two proteins was examined in the basal ganglia of rats and rhesus monkeys. In the striatum, CaBP immunoreactivity is localized to a subset of striatonigral projection neurons; CaBP-positive neurons are distributed in areas containing somatostatin-immunoreactive fibers and not in the complementary areas containing dense !t opiate-receptor binding. These biochemical labels mark, respectively, the matrix and patch compartments of the striatum. Previous

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Aerobic energy metabolism uses glucose and oxygen to produce all the energy needs of the brain. Several studies published over the last 13 years challenged the assumption that the activated brain increases its oxidative glucose metabolism to meet the increased energy demands. Neuronal function in rat hippocampal slices supplied with 4 mM glucose could tolerate a 15 min activation by a 5 mM concentration of the excitatory neurotransmitter glutamate (Glu), whereas slices supplied with 10 mM glucose could tolerate a 15 min activation by 20 mM Glu. However, in slices in which neuronal lactate use was inhibited by the lactate transporter inhibitor a-cyano-4-hydroxycinnamate (4-CIN), activation by Glu elicited a permanent loss of neuronal function, with a twofold to threefold increase in tissue lactate content. Inhibition of glycolysis with the glucose analog 2-deoxy-D-glucose (2DG) during the period of exposure to Glu diminished normal neuronal function in the majority of slices and significantly reduced the number of slices that exhibited neuronal function after activation. However, when lactate was added with 2DG, the majority of the slices were neuronally functional after activation by Glu. NMDA, a nontransportable Glu analog by the glial glutamate transporter, could not induce a significant increase in slice lactate level when administered in the presence of 4-CIN. It is suggested that the heightened energy demands of activated neurons are met through increased glial glycolytic flux. The lactate thus formed is a crucial aerobic energy substrate that enables neurons to endure activation.

Differential scanning calorimetry provides a new window into the plasma proteome. Plasma from normal individuals yields a characteristic, reproducible thermogram that appears to represent the weighted sum of denaturation profiles of the most abundant constituent plasma proteins. Plasma from diseased individuals yields dramatically different signature thermograms. Thermograms from individuals suffering from rheumatoid arthritis, systemic lupus, and Lyme disease were measured. Each disease appears to have a distinctive and characteristic thermogram. The difference in thermograms between normal and diseased individuals is not caused by radical changes in the concentrations of the most abundant plasma proteins but rather appears to result from interaction of as yet unknown biomarkers with the major plasma proteins. These results signal a novel use for calorimetry as a diagnostic tool.

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This study used the rat hippocampal slice preparation and the monocarboxylate transporter inhibitor, α‐cyano‐4‐hydroxycinnamate (4‐CIN), to assess the obligatory role that lactate plays in fueling the recovery of synaptic function after hypoxia upon reoxygenation. At a concentration of 500 µM, 4‐CIN blocked lactate‐supported synaptic function in hippocampal slices under normoxic conditions in 15 min. The inhibitor had no effect on glucose‐supported synaptic function. Of control hippocampal slices exposed to 10‐min hypoxia, 77.8 ± 6.8% recovered synaptic function after 30‐min reoxygenation. Of slices supplemented with 500 µM 4‐CIN, only 15 ± 10.9% recovered synaptic function despite the large amount of lactate formed during the hypoxic period and the abundance of glucose present before, during, and after hypoxia. These results indicate that 4‐CIN, when present during hypoxia and reoxygenation, blocks lactate transport from astrocytes, where the bulk of anaerobic lactate is formed, to neurons, where lactate is being utilized aerobically to support recovery of function after hypoxia. These results unequivocally validate that brain lactate is an obligatory aerobic energy substrate for posthypoxia recovery of function.

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