Reducing l-lactate release from hippocampal astrocytes by intracellular oxidation increases novelty induced activity in mice

Barbara Vaccari Cardoso, Alexey V. Shevelkin, Chantelle Terrillion, Olga Mychko, Valentina Mosienko, Sergey Kasparov, Mikhail Pletnikov, Anja G. Teschemacher

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1241-1250
Number of pages10
JournalGlia
Volume69
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • astrocytes
  • behavior
  • hippocampus
  • l-lactate
  • lactate oxidase
  • lentiviral vector
  • novelty

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Reducing l-lactate release from hippocampal astrocytes by intracellular oxidation increases novelty induced activity in mice'. Together they form a unique fingerprint.

Cite this