Astrocytes are in control of metabolic homeostasis in the brain and support and modulate neuronal function in various ways. Astrocyte-derived l-lactate (lactate) is thought to play a dual role as a metabolic and a signaling molecule in inter-cellular communication. The biological significance of lactate release from astrocytes is poorly understood, largely because the tools to manipulate lactate levels in vivo are limited. We therefore developed new viral vectors for astrocyte-specific expression of a mammalianized version of lactate oxidase (LOx) from Aerococcus viridans. LOx expression in astrocytes in vitro reduced their intracellular lactate levels as well as the release of lactate to the extracellular space. Selective expression of LOx in astrocytes of the dorsal hippocampus in mice resulted in increased locomotor activity in response to novel stimuli. Our findings suggest that a localized decreased intracellular lactate pool in hippocampal astrocytes could contribute to greater responsiveness to environmental novelty. We expect that use of this molecular tool to chronically limit astrocytic lactate release will significantly facilitate future studies into the roles and mechanisms of intercellular lactate communication in the brain.
Bibliographical noteFunding Information:
British Heart Foundation, Grant/Award Number: PG/18/8/33540: RG/19/5/34463; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Number: 206427/2014‐0; National Institute of Health, Grant/Award Numbers: DA‐041208, MH‐083728, MH‐094268; Northcott Devon Medical Trust Foundation, Grant/Award Number: TB/MG/NO5002; National Institute of Neurological Disorders and Stroke, Grant/Award Number: NS050274 Funding information
This work was supported by Science without Borders - CNPq (206427/2014-0 to BVC), BHF (PG/18/8/33540, RG/19/5/34463 to AGT), Northcott Devon Medical Trust Foundation Grant (TB/MG/NO5002 to VM); NIH (MH-083728, DA-041208, MH-094268 to MVP). The work at the JHU Neuroscience Multiphoton Imaging Core was supported by the National Institute of Neurological Disorders and Stroke grant (NS050274).
Science without Borders ‐ CNPq (206427/2014‐0 to BVC), BHF (PG/18/8/33540, RG/19/5/34463 to AGT), Northcott Devon Medical Trust Foundation Grant (TB/MG/NO5002 to VM); NIH (MH‐083728, DA‐041208, MH‐094268 to MVP). The work at the JHU Neuroscience Multiphoton Imaging Core was supported by the National Institute of Neurological Disorders and Stroke grant (NS050274). This work was supported by
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- lactate oxidase
- lentiviral vector