Direct measurement of oxidative metabolism in the living brain by microdialysis: a review.

This review summarizes microdialysis studies that address the question of which compounds serve as energy sources in the brain. Microdialysis was used to introduce 14C-labeled glucose, lactate, pyruvate, glutamate, glutamine, and acetate into the interstitial fluid of the brain to observe their metabolism to 14CO2. Although glucose uptake from the systemic system supplies the carbon source for these compounds, compounds synthesized from glucose by the brain are subject to recycling including complete metabolism to CO2.

Hormonal modulation of amino acid neurotransmitter metabolism in the arcuate nucleus of the adult female rat: a novel action of estradiol.

Morphological plasticity in response to estradiol is a hallmark of astrocytes in the arcuate nucleus. The functional consequences of these morphological changes have remained relatively unexplored. Here we report that in the arcuate nucleus estradiol significantly increased the protein levels of the two enzymes in the glutamate-glutamine cycle, glutamine synthetase and glutaminase.

Oxidation of (14)C-labeled compounds perfused by microdialysis in the brains of free-moving rats.

The oxidative capacity of the brain for alternate substrates, glucose, lactate, pyruvate, acetate, glutamate, and glutamine was determined by using microdialysis to infuse (14)C-labeled compounds into the interstitial fluid of adult rat brain and by collecting the brain-generated (14)CO(2) from the dialysis eluate. All compounds were readily oxidized. The recovery of (14)CO(2) was enhanced for those compounds metabolically close to entry into the TCA cycle or known to have a low interstitial concentration.

Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats.

Glucose is the primary carbon source to enter the adult brain for catabolic and anabolic reactions. Some studies suggest that astrocytes may metabolize glucose to lactate; the latter serving as a preferential substrate for neurons, especially during neuronal activation. The current study utilizes the aconitase inhibitor fluorocitrate to differentially inhibit oxidative metabolism in glial cells in vivo.

Formation of extracellular glutamate from glutamine: exclusion of pyroglutamate as an intermediate.

A 4.6-fold increase in interstitial glutamate was observed following the reverse microdialysis of 5 mM glutamine into the rat hippocampus. Two possible mechanisms of glutamine hydrolysis were examined: (a) an enzymatic glutaminase activity and (b) a non-enzymatic mechanism.

Large neutral amino acids auto exchange when infused by microdialysis into the rat brain: implication for maple syrup urine disease and phenylketonuria.

Maple syrup urine disease (MSUD) and phenylketonuria (PKU) are associated with accumulation of large neutral amino acids (LNAA) in blood and tissues and a decrease of other LNAA not directly related to the enzyme defects. One characteristic shared by both the elevated and decreased amino acids is that all are substrates for transport via the large neutral amino acid transporter. In this study, the blood brain barrier was effectively bypassed using microdialysis to determine the immediate effect of infused phenylalanine, tyrosine, 2-amino-2-norborane-carboxylic acid (BCH), and leucine and alpha-ketoisocaproate on extracellular levels of LNAA.