New Findings on Cellular Mechanism for Brain Energy May Improve Late-Life Brain Health

A key mechanism that detects when the brain needs an additional energy boost to support its activity has been identified in a study in mice and cells led by UCL scientists.

The findings, published in the journal Nature, could discover new therapies to maintain brain health and longevity, as other studies have found that brain energy metabolism can become impaired late in life and contribute to cognitive decline and the development of neurodegenerative disease.

Previous research has shown that astrocytes, a type of star-shaped brain cell, help supply energy to brain neurons. Astrocytes are glial cells, which are non-neuronal cells found in the central nervous system. When nearby neurons need more energy, astrocytes quickly activate their own glucose stores and metabolism. This process increases the production and release of lactate, which supplements the energy available for neurons in the brain.

In a series of experiments with mice and cell samples, researchers discovered specific receptors in astrocytes that detect and monitor neuronal activity. These receptors trigger a signalling pathway involving adenosine, a key molecule. They found that this pathway in astrocytes, which activates glucose metabolism to supply energy to neurons, is the same as the pathway that activates energy stores in muscles and the liver during exercise.

Adenosine helps astrocytes boost glucose metabolism and provide energy to neurons, ensuring that communication signals between brain cells continue smoothly, even under high energy demand or reduced energy supply.

When researchers deactivated these key astrocyte receptors in mice, the mice showed less effective brain activity, with significant impairments in overall brain metabolism, memory, and sleep. This demonstrated that the identified signalling pathway is crucial for learning, memory, and sleep.

"When our brain is active, like during mentally demanding tasks, it needs an immediate energy boost. However, the exact mechanisms ensuring this on-demand energy supply are not fully understood. Identifying this mechanism could help treat brain diseases where energy levels are low, such as neurodegeneration and dementia. Brain energy regulation declines with age and more rapidly in diseases like Alzheimer’s. Our study highlights a promising target for drugs to boost brain energy, protect brain function, maintain cognitive health, and promote brain longevity,” said the authors.

Reference: Theparambil, S.M., Kopach, O., Braga, A. et al. Adenosine signalling to astrocytes coordinates brain metabolism and function. Nature (2024). https://doi.org/10.1038/s41586-024-07611-w