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Related Experiment Video

Updated: Jun 19, 2026

Live-imaging of Mitochondrial System in Cultured Astrocytes
06:20

Live-imaging of Mitochondrial System in Cultured Astrocytes

Published on: November 16, 2021

NPAS3-regulated astrocyte mitochondrial bioenergetics is required for cognition.

Kateryna Murlanova1, Ksenia Novototskaya-Vlasova1, Shovgi Huseynov1

  • 1Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.

Science Advances
|June 17, 2026
PubMed

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Summary

Neuronal PAS domain protein 3 (NPAS3) regulates astrocyte mitochondrial function, impacting neuronal activity and cognitive performance. Restoring astrocyte metabolism with lactate may treat cognitive dysfunction in neuropsychiatric diseases.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Metabolic Research

Background:

  • Neuronal PAS domain protein 3 (NPAS3) is a transcription factor highly expressed in astrocytes.
  • NPAS3 variants are linked to cognitive dysfunction in neuropsychiatric conditions, but mechanisms are unclear.
  • Astrocytes play crucial roles in brain metabolism and neuronal support.

Purpose of the Study:

  • To investigate the role of NPAS3 in astrocyte mitochondrial bioenergetics.
  • To elucidate the cell type-specific mechanisms linking NPAS3 to cognitive function.
  • To explore potential glia-targeting therapeutic strategies for cognitive deficits.

Main Methods:

  • Selective deletion of the Npas3 gene in mature mouse astrocytes.
  • Analysis of mitochondrial gene expression, oxidative phosphorylation, and lactate production in astrocytes.

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Imaging Mitochondrial Ca2+ Uptake in Astrocytes and Neurons using Genetically Encoded Ca2+ Indicators (GECIs)
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Imaging Mitochondrial Ca2+ Uptake in Astrocytes and Neurons using Genetically Encoded Ca2+ Indicators (GECIs)

Published on: January 22, 2022

Related Experiment Videos

Last Updated: Jun 19, 2026

Live-imaging of Mitochondrial System in Cultured Astrocytes
06:20

Live-imaging of Mitochondrial System in Cultured Astrocytes

Published on: November 16, 2021

Imaging Mitochondrial Ca2+ Uptake in Astrocytes and Neurons using Genetically Encoded Ca2+ Indicators (GECIs)
07:46

Imaging Mitochondrial Ca2+ Uptake in Astrocytes and Neurons using Genetically Encoded Ca2+ Indicators (GECIs)

Published on: January 22, 2022

  • Assessment of neuronal excitability, dendritic spine density, and synaptic transmission in the medial prefrontal cortex (mPFC).
  • Behavioral testing using trace fear conditioning and rescue experiments with lactate treatment.

    • Main Results:

    • Npas3 deletion in astrocytes reduced mitochondrial glutamate carrier 2 expression, impairing oxidative phosphorylation and lactate production.
    • Astrocyte NPAS3 deficiency led to decreased neuronal excitability, dendritic spine density, and excitatory synaptic transmission in mPFC pyramidal neurons.
    • Mice with NPAS3-deficient astrocytes showed impaired trace fear conditioning, which was rescued by lactate administration.

    Conclusions:

    • NPAS3 is a critical regulator of astrocyte mitochondrial bioenergetics.
    • Astrocyte NPAS3-dependent metabolism directly influences neuronal function and cognitive behavior.
    • Targeting astrocyte metabolism, such as with lactate, offers a potential therapeutic avenue for cognitive dysfunction in neuropsychiatric diseases.