Astrocytes and neurons communicate via a monocarboxylic acid shuttle

Dirk Roosterman; Graeme S. Cottrell; Dirk Roosterman; Graeme S. Cottrell

doi:10.3934/Neuroscience.2020007

AIMS Neuroscience

2020, Volume 7, Issue 2: 94-106. doi: 10.3934/Neuroscience.2020007

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Astrocytes and neurons communicate via a monocarboxylic acid shuttle

Dirk Roosterman ^{1
,
,},
Graeme S. Cottrell ²

1.
Ruhr Universität Bochum, LWL-Hospital of Psychiatry, Bochum, Germany
2.
School of Pharmacy, University of Reading, Reading, RG6 6AP, UK

Received: 14 February 2020 Accepted: 13 April 2020 Published: 20 April 2020

Since formulation of the Astrocyte-Neuron Lactate Shuttle (ANLS) hypothesis in 1994, the hypothesis has provoked criticism and debate. Our review does not criticise, but rather integrates experimental data characterizing proton-linked monocarboxylate transporters (MCTs) into the ANLS. MCTs have wide substrate specificity and are discussed to be in protein complex with a proton donor (PD). We particularly focus on the proton-driven transfer of l-lactic acid (l-lacH) and pyruvic acid (pyrH), were PDs link MCTs to a flow of energy. The precise nature of the PD predicts the activity and catalytic direction of MCTs. By doing so, we postulate that the MCT4·phosphoglycerate kinase complex exports and at the same time in the same astrocyte, MCT1·carbonic anhydrase II complex imports monocarboxylic acids. Similarly, neuronal MCT2 preferentially imports pyrH. The repertoire of MCTs in astrocytes and neurons allows them to communicate via monocarboxylic acids. A change in imported pyrH/l-lacH ratio in favour of l-lacH encodes signals stabilizing the transit of glucose from astrocytes to neurons. The presented astrocyte neuron communication hypothesis has the potential to unite the community by suggesting that the exchange of monocarboxylic acids paves the path of glucose provision.
- astrocyte neuron glucose transit,
- astrocyte neuron lactate shuttle,
- enzyme complexes
Citation: Dirk Roosterman, Graeme S. Cottrell. Astrocytes and neurons communicate via a monocarboxylic acid shuttle[J]. AIMS Neuroscience, 2020, 7(2): 94-106. doi: 10.3934/Neuroscience.2020007

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Abstract

Since formulation of the Astrocyte-Neuron Lactate Shuttle (ANLS) hypothesis in 1994, the hypothesis has provoked criticism and debate. Our review does not criticise, but rather integrates experimental data characterizing proton-linked monocarboxylate transporters (MCTs) into the ANLS. MCTs have wide substrate specificity and are discussed to be in protein complex with a proton donor (PD). We particularly focus on the proton-driven transfer of l-lactic acid (l-lacH) and pyruvic acid (pyrH), were PDs link MCTs to a flow of energy. The precise nature of the PD predicts the activity and catalytic direction of MCTs. By doing so, we postulate that the MCT4·phosphoglycerate kinase complex exports and at the same time in the same astrocyte, MCT1·carbonic anhydrase II complex imports monocarboxylic acids. Similarly, neuronal MCT2 preferentially imports pyrH. The repertoire of MCTs in astrocytes and neurons allows them to communicate via monocarboxylic acids. A change in imported pyrH/l-lacH ratio in favour of l-lacH encodes signals stabilizing the transit of glucose from astrocytes to neurons. The presented astrocyte neuron communication hypothesis has the potential to unite the community by suggesting that the exchange of monocarboxylic acids paves the path of glucose provision.

Acknowledgments

Thank you to Prof. Luc Pellerin and Prof. Gerry Dienel for their help balancing ANC and for their interesting discussions.

Conflict of interest

The authors declare no conflict of interest.

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