Restoring 'Fuel' to Brain Cells Recovers Cognitive Function... Principle Behind Memory Maintenance Discovered [Reading Science]

Korea Brain Research Institute Identifies Role of Astrocyte 'NPAS3' Protein
Cognitive Function Declines When Lactate Supply Stops, Recovers with Resupply

A team of Korean researchers has identified the mechanism by which astrocytes, a type of glial cell in the brain, supply lactate as an energy source to neurons, thereby maintaining cognitive function. The team also confirmed that memory and learning abilities in mice with impaired cognitive function were restored when lactate was resupplied. This finding is expected to provide clues for developing new therapeutic strategies for neuropsychiatric disorders accompanied by cognitive impairment, such as autism and schizophrenia.

The Korea Brain Research Institute (KBRI) announced on June 25 that Dr. Juhyun Kim's research team, in collaboration with the University at Buffalo and Johns Hopkins School of Medicine, has discovered that the 'NPAS3' protein, expressed in astrocytes, is a key regulatory factor in maintaining normal cognitive function in the brain. The research findings were published in the latest issue of the international journal Science Advances.

Mechanism of Astrocyte Metabolic Dysfunction and Neuronal Function Decline Caused by NPAS3. While NPAS3 protein regulates the supply of lactate, the fuel for neurons, to maintain cognitive function, a decrease in NPAS3 reduces lactate supply, leading to cognitive and learning impairments. Provided by the research team

Although mutations in the NPAS3 gene have been known to be associated with cognitive decline observed in various neuropsychiatric disorders, including autism and schizophrenia, the specific cells involved and the mechanisms of action had not been elucidated.

The research team focused on the fact that NPAS3 is highly expressed in astrocytes. Astrocytes are glial cells that directly protect neurons and supply them with the energy they need.

The study found that NPAS3 acts as a key switch regulating mitochondrial energy metabolism in astrocytes. When the researchers removed NPAS3 from the astrocytes of mice, energy metabolism collapsed, leading to a significant decrease in the production of lactate, the primary fuel for neurons.

Astrocytes Serve as the 'Fuel Supply Center' for Neurons

As the supply of lactate decreased, both the electrical activity and excitatory signal transmission in prefrontal cortex neurons were reduced, and the density of dendritic spines—crucial for neural network connectivity—also declined. Consequently, cognitive function deteriorated. However, when lactate was resupplied, the previously impaired cognitive function was significantly restored.

Katerina Murlanova, Researcher at University at Buffalo, USA (First Author); Juhyun Kim, Ph.D., Korea Brain Research Institute (Corresponding Author); Mikhail Pletnikov, Professor at University at Buffalo, USA (Co-Corresponding Author). Provided by KBRI

This study is significant in that it demonstrated at the molecular level that astrocytes and neurons are closely connected through energy metabolism, and that NPAS3 is a key molecule regulating this process.

Juhyun Kim, Ph.D. at Korea Brain Research Institute, stated, "This research identifies the pathway through which abnormalities in NPAS3 can lead to dysfunction at the organelle, neural circuit, and behavioral levels. We expect these findings to provide important clues for understanding the pathogenesis of neuropsychiatric disorders such as autism and schizophrenia, and for developing new therapeutic strategies in the future."

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