Summary: Scientists have identified a key mechanism that detects when the brain needs an energy boost, involving astrocytes and the adenosine molecule. This discovery could lead to new therapies to maintain 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 supply pathways, ensuring efficient brain function. This breakthrough offers a potential treatment for conditions such as Alzheimer’s disease.
Key facts:
- Astrocytes play a key role in supplying energy to neurons during highly demanding activities.
- The adenosine molecule is essential for the activation of astrocyte glucose metabolism.
- Disruption of this energy-boosting mechanism impairs brain function, memory and sleep.
Source: UCL
A key mechanism that detects when the brain needs extra energy support to fuel its activity has been identified in a mouse and cell study led by UCL scientists.
The researchers say their findings, published in Naturecould inform new therapies to maintain brain health and longevity, as other studies have found that the brain’s energy metabolism can become impaired in late life and contribute to cognitive decline and the development of neurodegenerative diseases.
Lead author Professor Alexander Gourine (UCL Neuroscience, Physiology & Pharmacology) said: “Our brain is made up of billions of nerve cells that work together to coordinate numerous functions and perform complex tasks such as controlling movement, learning and forming memories. All these calculations are very energy intensive and require a continuous supply of nutrients and oxygen.
“When our brain is more active, for example when we perform a mentally demanding task, our brain needs an immediate boost of energy, but the precise mechanisms that ensure the local supply of metabolic energy to active areas of the brain on demand are not fully functional. understood.”
Previous research has shown that numerous brain cells called astrocytes appear to play a role in providing brain neurons with the energy they need. Shaped like stars, astrocytes are a type of glial cell, which are non-neuronal cells found in the central nervous system.
When neighboring neurons need to increase their energy supply, astrocytes jump into action by rapidly activating their own glucose stores and metabolism, leading to increased lactate production and release. Lactate replenishes the supply of energy that is readily available for use by neurons in the brain.
Professor Gourine explained: “In our study, we discovered how precisely astrocytes are able to monitor the energy consumption of 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 an essential molecule called adenosine.
The researchers discovered that the metabolic signaling pathway activated by adenosine in astrocytes is exactly the same as the pathway that obtains energy stores in the muscles and liver, for example when we exercise.
Adenosine activates astrocyte glucose metabolism and neuronal energy delivery to ensure that synaptic function (neurotransmitters carrying communication signals between cells) continues at a rapid pace 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, demonstrating that the signaling pathway they identified is vital to processes such as .learning, memory and sleep.
First and co-corresponding author Dr Shefeeq Theparambil, who started the study 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 where brain energy is downregulated, e.g. like neurodegeneration and dementia.”
Professor Gourine added: “We know that the brain’s energy homeostasis gradually breaks down with 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 for salvaging brain energy to protect brain function, maintain cognitive health, and promote brain longevity.”
Funding: 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 news from neuroscience research
Author: Chris Lane
Source: UCL
Contact: Chris Lane – UCL
Picture: Image is credited to Neuroscience News
Original Research: Open access.
“Adenosine signaling to astrocytes coordinates brain metabolism and function” Alexander Gourine et al. Nature
Abstract
Adenosine signaling to astrocytes coordinates brain metabolism and function
The brain’s computation, carried out by billions of nerve cells, relies on an adequate and uninterrupted supply of nutrients and oxygen.
Astrocytes, the ubiquitous glial neighbors of neurons, control brain glucose uptake and metabolism, but the precise mechanisms of the 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 astrocytic A2B receptors. Stimulation of A2B receptors recruits canonical cyclic adenosine 3′,5′-monophosphate protein kinase
A signaling pathway leading to the rapid activation of astrocyte glucose metabolism and the release of lactate, which replenishes the extracellular supply 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, particularly under conditions of high energy demand or reduced energy supply.
Reduction of A2B receptor expression in astrocytes led to a major 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 astrocytic sensor of neuronal activity and show that cAMP signaling in astrocytes tunes the brain’s energy metabolism to support essential functions such as sleep and memory.