Brain energy boost mechanism discovered

Resume: Researchers have identified a key mechanism that senses when the brain needs an energy boost, involving astrocytes and the molecule adenosine. The 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, which ensures efficient brain function. This breakthrough offers potential treatments for conditions such as Alzheimer’s disease.

Key Facts:

  1. Astrocytes play a crucial role in supplying energy to neurons during high-energy activities.
  2. The molecule adenosine is essential for the activation of glucose metabolism in astrocytes.
  3. If this energy-boosting mechanism is disrupted, it will affect brain function, memory and sleep.

Source: UCL

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

The scientists say their findings, published in Naturecould lead to new therapies to maintain brain health and longevity. Other studies have shown that the brain’s energy metabolism can become disrupted in old age, contributing to cognitive decline and the development of neurodegenerative diseases.

This shows brains.
Adenosine activates glucose metabolism in astrocytes and energy supply in neurons to ensure that synaptic function (neurotransmitters that transmit communication signals between cells) continues at a high rate under conditions of high energy demand or reduced energy supply. Credit: Neuroscience News

Lead author Professor Alexander Gourine (UCL Neuroscience, Physiology & Pharmacology) said: “Our brains are made up of billions of nerve cells, which work together to coordinate countless functions and carry out complex tasks such as controlling movement, learning and forming memories. All of these computations are very energy-intensive and require a constant supply of nutrients and oxygen.

“When our brains are more active, such as when we are performing a mentally demanding task, our brains need an immediate energy boost, but the exact mechanisms by which active brain areas are supplied with local metabolic energy on demand are not yet fully understood.”

Previous research has shown that numerous brain cells called astrocytes appear to play a role in supplying the brain’s neurons with the energy they need. Astrocytes, which are shaped like stars, are a type of glial cell, which are non-neuronal cells found in the central nervous system.

When neighboring neurons require an increase in energy supply, astrocytes spring into action by rapidly activating their own glucose stores and metabolism, leading to the increased production and release of lactate. Lactate replenishes the energy supply that is immediately available for use by neurons in the brain.

Professor Gourine explains: “In our research, we have discovered how astrocytes can precisely monitor the energy consumption of their neighbouring nerve cells and initiate this process that provides extra chemical energy to busy brain areas.”

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 activate a signaling pathway involving a key molecule called adenosine.

The researchers found that the metabolic signaling pathway activated by adenosine in astrocytes is exactly the same as the pathway that draws on energy stores in muscles and the liver, for example when we exercise.

Adenosine activates glucose metabolism in astrocytes and the energy supply of neurons. This keeps synaptic function (neurotransmitters that transmit communication signals between cells) functioning properly, even with high energy demand or low energy supply.

The researchers found that when they deactivated key astrocyte receptors in mice, the animals’ brain activity was less effective. This led to significant impairments in overall 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 began the study at UCL before moving to Lancaster University, said: “Identifying this mechanism could have wider implications as it could provide a way to treat brain diseases where brain energy is suppressed, such as neurodegeneration and dementia.”

Professor Gourine added: “We know that brain energy homeostasis is gradually disrupted as we age and that this process is accelerated during the development of neurodegenerative diseases such as Alzheimer’s.

“Our research identifies an attractive, directly deliverable target and therapeutic opportunity for rescuing brain energy with the goal of protecting brain function, preserving cognitive health, and promoting brain longevity.”

Financing: The researchers received support from Wellcome and the research 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 Laan
Source: UCL
Contact: Chris Lane – UCL
Image: The image is attributed to Neuroscience News

Original research: Open access.
“Adenosine signaling to astrocytes coordinates brain metabolism and function” by Alexander Gourine et al. Nature


Adenosine signaling to astrocytes coordinates brain metabolism and function

Brain computations performed by billions of nerve cells depend on an adequate and uninterrupted supply of nutrients and oxygen.

Astrocytes, the ubiquitous glial neighbors of neurons, regulate glucose uptake and metabolism in the brain. However, 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 neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3′,5′-monophosphate protein kinase

A signaling pathway that leads to rapid activation of glucose metabolism in astrocytes and the release of lactate, which replenishes the extracellular supply of readily available energy substrates.

Experimental mouse models in which the gene encoding A2B receptors in astrocytes was conditionally deleted showed that adenosine-mediated metabolic signaling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply.

Decreased A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, impaired synaptic plasticity in the hippocampus, severely disrupted recognition memory, and disturbed sleep.

These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and demonstrate that cAMP signaling in astrocytes tunes brain energy metabolism to support fundamental functions such as sleep and memory.

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