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Expression of Microbial Enzymes in Mammalian Astrocytes to Modulate Lactate Release

Cardoso, BV; Barrera, I; Mosienko, V; Gourine, A; Kasparov, S; Teschemacher, AG; (2021) Expression of Microbial Enzymes in Mammalian Astrocytes to Modulate Lactate Release. Brain Sciences , 11 (8) , Article 1056. 10.3390/brainsci11081056. Green open access

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Abstract

Astrocytes support and modulate neuronal activity through the release of L-lactate. The suggested roles of astrocytic lactate in the brain encompass an expanding range of vital functions, including central control of respiration and cardiovascular performance, learning, memory, executive behaviour and regulation of mood. Studying the effects of astrocytic lactate requires tools that limit the release of lactate selectively from astrocytes. Here, we report the validation in vitro of novel molecular constructs derived from enzymes originally found in bacteria, that when expressed in astrocytes, interfere with lactate handling. When lactate 2-monooxygenase derived from M. smegmatis was specifically expressed in astrocytes, it reduced intracellular lactate pools as well as lactate release upon stimulation. D-lactate dehydrogenase derived from L. bulgaricus diverts pyruvate towards D-lactate production and release by astrocytes, which may affect signalling properties of lactate in the brain. Together with lactate oxidase, which we have previously described, this set of transgenic tools can be employed to better understand astrocytic lactate release and its role in the regulation of neuronal activity in different behavioural contexts.

Type: Article
Title: Expression of Microbial Enzymes in Mammalian Astrocytes to Modulate Lactate Release
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/brainsci11081056
Publisher version: http://dx.doi.org/10.3390/brainsci11081056
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: astrocytes; lactate; gliotransmitter; viral vectors
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10134202
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