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 for maintaining brain health and longevity, particularly in combating cognitive decline and neurodegenerative diseases.
The study found that astrocytes monitor neuronal activity and activate energy supply pathways, ensuring efficient brain function. This discovery offers potential treatments for conditions such as Alzheimer’s disease.
Key facts:
- Astrocytes play a crucial role in supplying energy to neurons during high-demand 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: UCLA
A key mechanism that detects when the brain needs an extra boost of energy to sustain its activity has been identified in a study in mice and cells led by UCL scientists.
Scientists say their findings, published in Naturemay inform new therapies to maintain brain health and longevity, as other studies have found that the brain’s energy metabolism can be impaired late in life and contribute to cognitive decline and the development of neurodegenerative diseases.
Lead author Professor Alexander Gourine (UCL Neuroscience, Physiology and Pharmacology) said: “Our brain is made up of billions of nerve cells, which work together to coordinate multiple functions and carry out complex tasks such as movement control, learning and memory formation. memories. All this calculation requires a lot of energy and requires an uninterrupted supply of nutrients and oxygen.
“When our brain is most active, such as when we are performing a fixed mental task, our brain needs an immediate boost of energy, but the precise mechanisms that ensure the on-demand local supply of metabolic energy to active brain regions they are not completely. 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. Astrocytes, shaped like stars, 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 jump into action by rapidly activating their glucose stores and metabolism, leading to increased lactate production and release. Lactate replenishes the energy reserve that is readily available for use by neurons in the brain.
Professor Gourine explained: “In our study, we have understood how exactly astrocytes are able to monitor the energy use of their neighboring nerve cells and initiate this process that delivers additional chemical energy to busy brain regions.”
In a series of experiments using mouse models and cell samples, the researchers identified a set of specific receptors on astrocytes that can detect and monitor neuronal activity and trigger a signaling pathway involving a crucial molecule called adenosine.
The researchers found 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 astrocyte glucose metabolism and neuronal energy supply to ensure that synaptic function (the neurotransmitters that pass communication signals between cells) continues rapidly under conditions of high energy demand or reduced energy supply.
The researchers found that when they disabled key astrocyte receptors in mice, the animal’s brain activity was less effective, including significant impairments in global brain metabolism, memory and sleep disruption, demonstrating that the signaling pathway they identified is vital for processes such as learning, memory and sleep.
First author 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 low, such as like neurodegeneration and dementia.”
Professor Gourine added: “We know that the brain’s energy homeostasis is progressively impaired during 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 a therapeutic opportunity for salvaging brain energy to protect brain function, preserve cognitive health, and promote brain longevity.”
Funding: The researchers were supported by Wellcome and the study involved scientists at 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: UCLA
Contact: Chris Lane – UCL
Image: Image is credited to Neuroscience News
Original research: Open access.
“Adenosine signaling in astrocytes coordinates brain metabolism and function” by Alexander Gourine et al. Nature
ABSTRACT
Adenosine signaling in astrocytes coordinates brain metabolism and function
The brain’s computation performed by billions of nerve cells relies on a sufficient and uninterrupted supply of nutrients and oxygen.
Astrocytes, the ubiquitous glial neighbors of neurons, regulate glucose uptake and metabolism in the brain, but the precise mechanisms of metabolic coupling between neurons and astrocytes that provide on-demand support of neuronal energy needs are not fully understood.
Here we show, using in vitro and in vivo experimental animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulatory 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 pool of readily available energy substrates.
Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes demonstrated that adenosine-mediated metabolic signaling is essential for maintaining synaptic function, particularly under conditions of high energy demand or reduced energy supply.
Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severe recognition memory impairment, and sleep disruption.
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 its basic functions such as sleep and memory.
