2026-06-18 バッファロー大学（UB）
The gene NPAS3 controls how brain support cells, or astrocytes, generate energy in their mitochondria (shown here). This energy production is necessary for normal thinking, learning and memory.
＜関連情報＞
- https://www.buffalo.edu/news/releases/2026/06/NPAS3-study-brain-health.html
- https://www.science.org/doi/10.1126/sciadv.adt2527
NPAS3によって制御されるアストロサイトのミトコンドリア生体エネルギーは認知機能に必要である NPAS3-regulated astrocyte mitochondrial bioenergetics is required for cognition
Kateryna Murlanova, Ksenia Novototskaya-Vlasova, Shovgi Huseynov, Olga Pletnikova, […] , and Mikhail V. Pletnikov
Science Advances Published:17 Jun 2026
DOI:https://doi.org/10.1126/sciadv.adt2527
Abstract
The basic helix-loop-helix transcription factor neuronal PAS (Per, Arnt, Sim) domain protein 3 (NPAS3) provides transcriptional regulation of metabolic pathways and is highly expressed in astrocytes. NPAS3 variants have been associated with cognitive dysfunction under several neuropsychiatric conditions, but the underlying brain cell type–specific mechanisms remain obscure. Here, we report that NPAS3 is a key regulator of mitochondrial bioenergetics in astrocytes in the mouse brain. Selective deletion of Npas3 in mature astrocytes decreases expression of mitochondrial glutamate carrier 2 involved in glutamate oxidation, leading to reduced oxidative phosphorylation and lactate production in astrocytes. This deficit reduces intrinsic excitability, dendritic spine density, and excitatory synaptic transmission of medial prefrontal cortex (mPFC) pyramidal neurons. Mice with Npas3-deficient mPFC astrocytes exhibit impaired trace fear conditioning, which is rescued by lactate treatment. Thus, the present study demonstrates a mechanistic link between NPAS3-dependent astrocyte mitochondrial bioenergetics and cognitive function and provides insights for glia-targeting treatment of cognitive dysfunction in neuropsychiatric disease.
