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REPORT

The Cerebral Tricarboxylic Acid Cycles

T. B. Rodrigues . S. Cerda´n

1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

2 The Cerebral Tricarboxylic Acid Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 2.1 Regionalization and Subcellular Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 2.2 Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 3 3.1 3.2 3.3

Methodologies to Investigate Tricarboxylic Acid Cycle Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Radioactive Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Nuclear Magnetic Resonance Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Dual Photon NADH Fluorescence Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

4 4.1 4.2 4.3 4.4 4.5

The Cerebral Tricarboxylic Acid Cycles During Cerebral Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 The Metabolic Coupling Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 13 C NMR Evidences and the Neuronal Tricarboxylic Acid Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 The Astroglial Tricarboxylic Acid Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 The Redox Switch and the Redox Coupling Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 NADH Balance in Neurons and Glia During Cerebral Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

5

Concluding Remarks and Future Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

#

Springer-Verlag Berlin Heidelberg 2007

64

1.4

The cerebral tricarboxylic acid cycles

Abstract: We review the operation of the cerebral tricarboxylic acid (TCA) cycles in the neuronal and glial compartments of the adult rat brain, with an emphasis on the mechanisms underlying intercellular oxidative coupling during glutamatergic neurotransmission. We begin with an update of the enzymatic properties, gene location, regulation, and regional distribution of the enzymes involved. Then, we describe the main methodologies used to investigate TCA cycle activity in vitro and in vivo such as au

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