Glutamate reduces glucose utilization while concomitantly enhancing AQP9 and MCT2 expression in cultured rat hippocampal neurons.

Fabio Tescarollo,Luciene Covolan,Luc Pellerin

doi:10.3389/fnins.2014.00246

Abstract

The excitatory neurotransmitter glutamate has been reported to have a major impact on brain energy metabolism. Using primary cultures of rat hippocampal neurons, we observed that glutamate reduces glucose utilization in this cell type, suggesting alteration in mitochondrial oxidative metabolism. The aquaglyceroporin AQP9 and the monocarboxylate transporter MCT2, two transporters for oxidative energy substrates, appear to be present in mitochondria of these neurons. Moreover, they not only co-localize but they interact with each other as they were found to co-immunoprecipitate from hippocampal neuron homogenates. Exposure of cultured hippocampal neurons to glutamate 100 μM for 1 h led to enhanced expression of both AQP9 and MCT2 at the protein level without any significant change at the mRNA level. In parallel, a similar increase in the protein expression of LDHA was evidenced without an effect on the mRNA level. These data suggest that glutamate exerts an influence on neuronal energy metabolism likely through a regulation of the expression of some key mitochondrial proteins.

Highlights

The human brain represents only 2% of the total body weight but it accounts for a much larger proportion of the total energy expenditures of the organism (Magistretti, 1999)
We aimed to determine (1) whether glutamate modulates glucose utilization in rat hippocampal neurons, (2) if AQP9 and MCT2 can be coexpressed by neuronal mitochondria, and (3) if glutamate could alter the expression of AQP9 and/or MCT2 in the same neuronal population
The expression of the aquaglyceroporin AQP9 and the monocarboxylate transporter MCT2 which are involved in the transport of oxidative substrates was investigated in this preparation

Summary

Introduction

The human brain represents only 2% of the total body weight but it accounts for a much larger proportion of the total energy expenditures of the organism (Magistretti, 1999). A major part of glucose uptake taking place in an activated brain region and visualized by functional brain imaging is due to astrocytic utilization (Pellerin and Magistretti, 1996b, 2012; Figley and Stroman, 2011) Such a view is reinforced by recent observations made ex vivo and in vivo. It was demonstrated in cerebellar slices using fluorescent glucose analogs that both glucose transport and metabolism occur preferentially in Bergmann glia over Purkinje cells while the same observation was made for astrocytes over neurons in hippocampal slices (Barros et al, 2009; Jakoby et al, 2014) It was shown in experiments performed in anesthetized rats that whisker stimulation caused a significant increase of glucose uptake in astrocytes, but not in neurons, in the activated somatosensory cortex (Chuquet et al, 2010). While these data indicate that a prominent part of glucose utilization take place in astrocytes, they suggest that active neurons must obtain an alternative energy substrate to cover their enhanced energy needs

Objectives

Methods

Results

Conclusion