Summary: The researchers identified a key mechanism that detects when the brain needs an energy boost involving astrocytes and the molecule adenosine. This discovery could lead to new therapies to support brain health and longevity, particularly in the fight against cognitive decline and neurodegenerative diseases.
The study found that astrocytes monitor neuronal activity and activate energy delivery pathways, ensuring efficient brain function. This breakthrough offers potential treatments for conditions such as Alzheimer’s disease.
Key facts:
- Astrocytes play a critical role in supplying energy to neurons during high-demand activities.
- The molecule adenosine is essential for the activation of glucose metabolism in astrocytes.
- Disruption of this energy-boosting mechanism impairs brain function, memory, and sleep.
source: UCL
A key mechanism that detects when the brain needs an extra energy boost to keep it going has been identified in a mouse and cell study led by UCL scientists.
The scientists say their findings, published in Naturemay inform new therapies to maintain brain health and longevity, as other studies have found that brain energy metabolism can be disrupted at the end of life and contribute to cognitive decline and the development of neurodegenerative diseases.
Lead author Professor Alexander Gurin (UCL Neuroscience, Physiology & Pharmacology) said: “Our brains are made up of billions of nerve cells that work together, coordinating multiple functions and performing complex tasks such as movement control, learning and memory formation. All these calculations require a lot of energy and require a continuous supply of nutrients and oxygen.
“When our brain is more active, such as when we are performing a mentally demanding task, our brain needs an immediate boost of energy, but the exact mechanisms that provide a local supply of on-demand metabolic energy to active areas of the brain are not fully understood .”
Previous research has shown that a variety of brain cells called astrocytes appear to play a role in providing brain neurons with the energy they need. Star-shaped astrocytes are a type of glial cell, which are non-neuronal cells found in the central nervous system.
When neighboring neurons need an increase in energy supply, astrocytes spring into action by rapidly activating their own glucose stores and metabolism, resulting in increased lactate production and release. Lactate replenishes a reserve of energy that is readily available for use by neurons in the brain.
Professor Gourine explained: “In our research, we have understood exactly how astrocytes are able to monitor the energy use of their neighboring nerve cells and start this process, which supplies additional chemical energy to busy areas of the brain.”
In a series of experiments using mouse models and cell samples, the researchers identified a set of specific receptors in astrocytes that can detect and monitor neuronal activity and trigger a signaling pathway involving a key molecule called adenosine.
The researchers discovered that the metabolic signaling pathway activated by adenosine in astrocytes is exactly the same as the pathway that recruits energy stores in muscle and liver, for example when we exercise.
Adenosine activates glucose metabolism in astrocytes and energy delivery to neurons to ensure that synaptic function (neurotransmitters transmitting communication signals between cells) continues rapidly under conditions of high energy demand or reduced energy supply.
The researchers found that when they deactivated key astrocyte receptors in mice, the animal’s brain activity was less efficient, including significant impairments in global brain metabolism, memory and sleep disruption, thereby demonstrating that the signaling pathway they identified is vital for processes such as learning, memory and sleep.
First and co-correspondent Dr Shefeeq Theparambil, who started the research at UCL before moving to Lancaster University, said: “Identifying this mechanism could have wider implications as it could be a way to treat brain diseases in which brain energy is down-regulated, such as neurodegeneration and dementia.
Professor Gourine added: “We know that brain energy homeostasis is progressively disrupted in aging and this process is accelerated during the development of neurodegenerative diseases such as Alzheimer’s disease.
“Our study identifies an attractive, easily druggable target and therapeutic opportunity to rescue brain energy to protect brain function, maintain cognitive health, and promote brain longevity.”
Financing: The researchers were supported by Wellcome and the study involved scientists from UCL, Lancaster University, Imperial College London, King’s College London, Queen Mary University of London, University of Bristol, University of Warwick and University of Colorado.
About this neuroscience research news
Author: Chris Lane
source: UCL
Contact: Chris Lane – UCL
Image: Image credit: Neuroscience News
Original Research: Free access.
“Adenosine signaling to astrocytes coordinates brain metabolism and function” by Alexander Gourine et al. Nature
Summary
Adenosine signaling to astrocytes coordinates brain metabolism and function
The brain’s computations, carried out by billions of nerve cells, rely on an adequate and continuous supply of nutrients and oxygen.
Astrocytes, the ubiquitous glial neighbors of neurons, govern glucose uptake and metabolism in the brain, but the precise mechanisms of metabolic coupling between neurons and astrocytes that provide on-demand support for neuronal energy needs are not fully understood.
Here, we show using experimental in vitro and in vivo animal models that neuronal activity-dependent metabolic activation of astrocytes is mediated by the neuromodulator adenosine acting on astrocyte A2B receptors. Stimulation of A2B receptors recruits canonical cyclic adenosine 3′,5′-monophosphate-protein kinase
A signaling pathway leading to rapid activation of astrocyte glucose metabolism and release of lactate that replenishes the extracellular pool of readily available energy substrates.
Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes have shown that adenosine-mediated metabolic signaling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply.
Knockdown of A2B receptor expression in astrocytes resulted in significant reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory, and disrupted sleep.
These data identify the adenosine A2B receptor as an astrocyte sensor of neuronal activity and show that cAMP signaling in astrocytes tunes the brain’s energy metabolism to support its essential functions such as sleep and memory.
