Preserved Cerebral Oxygen Metabolism in Astrocytic Dysfunction: A Combination Study of 15O-Gas PET with 14C-Acetate Autoradiography.

Carla Mari Macaisa,Eku Shimosegawa,Yuwei Liu,Yasukazu Kanai,Genki Horitsugi,Tadashi Watabe,Jun Hatazawa,Victor Romanov,Hiroki Kato

doi:10.3390/brainsci9050101

Abstract

Fluorocitrate (FC) is a specific metabolic inhibitor of the tricarboxylic acid (TCA) cycle in astrocytes. The purpose of this study was to evaluate whether inhibition of the astrocyte TCA cycle by FC would affect the oxygen metabolism in the rat brain. At 4 h after the intracranial FC injection, the rats (n = 9) were investigated by 15O-labeled gas PET to measure the cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV). After the 15O-gas PET, the rats were given an intravenous injection of 14C-acetate for autoradiography. 15O-gas PET showed no significant differences in any of the measured parameters between the ipsilateral and contralateral striatum (high dose group: CBF (54.4 ± 8.8 and 55.3 ± 11.6 mL/100 mL/min), CMRO2 (7.0 ± 0.9 and 7.1 ± 1.2 mL/100 mL/min), OEF (72.0 ± 8.9 and 70.8 ± 8.2%), and CBV (4.1 ± 0.8 and 4.2 ± 0.9 mL/100 mL), respectively). In contrast, the 14C-acetate autoradiography revealed a significant inhibition of the astrocyte metabolism in the ipsilateral striatum. The regional cerebral oxygen consumption as well as the hemodynamic parameters were maintained even in the face of inhibition of the astrocyte TCA cycle metabolism in the rat brain.

Highlights

Astrocytes or astroglia are the largest and most numerous of the glial cells in the central nervous system; they provide support, nourishment, and protection for neurons [1]
The glutamate/gamma-aminobutyric acid (GABA)/glutamine cycle is a metabolic pathway in which glutamate or GABA released from neurons is taken up by the astrocytes; in turn, astrocytes release glutamine that is taken up by the neurons for use as a precursor for the synthesis of glutamate or GABA
The primary purpose of this study was to evaluate whether inhibition of the astrocyte tricarboxylic acid (TCA) cycle by FC would affect the regional oxygen metabolism in the rat brain

Summary

Introduction

Astrocytes or astroglia are the largest and most numerous of the glial cells in the central nervous system; they provide support, nourishment, and protection for neurons [1]. Two specific types of interactions are believed to exist between neurons and astrocytes: the glutamate–glutamine cycle and the lactate shuttle [5]. The tricarboxylic acid (TCA) cycle is suppressed in the neurons and astrocytes due to the oxygen metabolism decline [1].

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