summary: A new study introduced a new bioluminescent imaging technique to observe the movement of oxygen in the brains of mice. Inspired by firefly proteins, the technique reveals broad patterns in oxygen distribution in real time, providing insight into conditions such as hypoxia caused by strokes and heart attacks.
Additionally, we are investigating how a sedentary lifestyle may increase the risk of Alzheimer’s disease by detecting “hypoxic pockets” or areas of temporary oxygen deprivation. This study paves the way for a deeper understanding of brain hypoxia-related diseases and for testing therapeutic interventions.
Important facts:
- New bioluminescent imaging technology now allows scientists to observe the movement of oxygen in the brain, providing a detailed view in real time.
- The method shows that regions of the brain can experience temporary oxygen deprivation known as “hypoxic pockets,” which are more common in sedentary conditions and are associated with Alzheimer’s disease. may be associated with an increased risk of
- This study, which bridges research from the University of Rochester and the University of Copenhagen, could revolutionize our understanding of diseases associated with brain hypoxia and pave the way for new therapeutic interventions.
sauce: University of Copenhagen
The human brain consumes a huge amount of energy, and most of that energy is generated through metabolism, which requires oxygen. Efficient and timely oxygen allocation and delivery is therefore critical for healthy brain function, but the exact mechanism of this process remains largely hidden from scientists.
New bioluminescent imaging technology described in today’s journal sciencecreated highly detailed and visually impressive images showing the movement of oxygen within the brains of mice.
The method can be easily replicated in other labs, allowing researchers to more precisely study forms of hypoxia, such as the denial of oxygen to parts of the brain that occurs during strokes and heart attacks. Become. We are already gaining insight into why a sedentary lifestyle increases the risk of diseases such as Alzheimer’s disease.
“This study shows that we can continuously monitor changes in oxygen levels in large regions of the brain,” said Miken, co-director of the Center for Translational Neurology, based at both the University of Rochester and the University of Rochester. Nedergaard says. Copenhagen.
“This gives us a much more detailed view of what’s happening in the brain in real time, allowing us to detect previously undetectable transients that reflect changes in blood flow that can cause neurological damage. It allows us to identify areas of hypoxia,” says Miken Nedergaard.
Fireflies and accidental science
The new method utilizes a photoprotein that is chemically similar to the bioluminescent protein found in fireflies. These proteins are used in cancer research and rely on viruses that tell cells to produce light-emitting proteins in the form of enzymes. When the enzyme encounters its substrate, called furimazine, a chemical reaction produces light.
Like many important scientific discoveries, using this process to image oxygen in the brain happened by chance. Assistant Professor Felix Weinrich from the Center for Translational Neuroscience at the University of Copenhagen originally intended to use luminescent proteins to measure calcium activity in the brain. It turned out that there was an error in the production of the protein, delaying the research for several months.
While waiting for a new batch from the manufacturer, Felix Beinlich decided to proceed with experiments to test and optimize the monitoring system. The virus was used to deliver enzyme production instructions to astrocytes, the brain’s ubiquitous supporting cells that maintain neuron health and signaling functions, and the substrate was injected directly into the brain.
The recordings revealed activity identified by variations in the intensity of bioluminescence. The researchers speculated that this reflected the presence and concentration of oxygen, something they would later confirm. “The chemical reaction in this case relied on oxygen, so when the enzyme, substrate and oxygen are present, the system starts emitting light,” says Felix Weinrich.
Existing oxygen monitoring techniques provide information about small areas of the brain, but the researchers looked at the entire mouse cortex in real time. The intensity of bioluminescence corresponds to oxygen concentration, and the researchers demonstrated this by changing the amount of oxygen in the air the animals were breathing.
Changes in light intensity also corresponded to sensory processing. For example, when stimulating a mouse’s whiskers with a puff of air, researchers could see the corresponding sensory areas of the brain light up.
‘Hypoxic pockets’ may indicate Alzheimer’s disease risk
The brain cannot survive long without oxygen. This is demonstrated by the neurological damage that occurs immediately after a stroke or heart attack. But what happens when a small part of the brain is deprived of oxygen for a short period of time?
This question wasn’t even asked by researchers until the team in Nedergaard’s lab began taking a closer look at the new recordings. While observing the mice, the researchers observed that certain small areas of the brain intermittently darkened, sometimes for a few seconds. This means that the oxygen supply is cut off.
Oxygen circulates throughout the brain through a vast network of arteries and smaller capillaries, or microvessels, that permeate the brain tissue.
Through a series of experiments, the researchers were able to determine that oxygen was cut off by capillary stall, which occurs when white blood cells temporarily block microvessels, preventing the passage of oxygen carrying red blood cells.
These areas, which the researchers termed “hypoxic pockets,” were more present in the mice’s brains when they were at rest compared to when they were active. Capillary stalling is thought to increase with age and has also been observed in models of Alzheimer’s disease.
“A variety of diseases related to hypoxia in the brain, such as Alzheimer’s disease, vascular dementia, and long-term exposure to COVID-19, and a sedentary lifestyle, aging, high blood pressure, and other factors contribute to these “This opens the door to studying how it contributes to disease,” says Miken Nedergaard. And I’ll add this:
“It also provides tools to test different drugs and types of exercise that can improve blood vessel health and slow the progression to dementia.”
Other authors include Antonios Asiminas of the University of Copenhagen, Hajime Hirase of the University of Rochester, Verena Unthiet, Zuzanna Božalovska, Virginia Puller, and Björn Sigurdsson of the University of Copenhagen, as well as Vincenzo Timmel, Lukas Gehrig, and Michael・Includes H. Graybar. University of Applied Sciences and Arts Northwestern Switzerland.
Funding: This research was supported by funding from the National Institute of Neurological Disorders and Stroke, the Miriam and Dr. Sheldon G. Adelson Medical Research Foundation, the Novo Nordisk Foundation, the Lundbeck Foundation, the Danish Independent Research Fund, and the U.S. Army Research Office. It was done.
About this neuroscience research news
author: Reba Pollack
sauce: University of Copenhagen
contact: Riva Pollack – University of Copenhagen
image: Image credited to Neuroscience News
Original research: Closed access.
“Oxygen imaging of hypoxic pockets in mouse cerebral cortexWritten by Miken Nedergaard et al. science
abstract
Oxygen imaging of hypoxic pockets in mouse cerebral cortex
When blood flow to the brain stops, people lose consciousness within seconds. Disruption of oxidative phosphorylation can be fatal within minutes because the brain cannot store oxygen. However, only rudimentary knowledge exists regarding cortical partial oxygen tension (Pah2) Dynamics under physiological conditions.
Here we introduce green-enhanced nanolanthanum (GeNL), a genetically encoded bioluminescent oxygen indicator. Pah2 Imaging.
We revealed the existence of spontaneous, spatially defined “hypoxic pockets” in awake, behaving mice and demonstrated that they are associated with the abolition of local capillary flow. Exercise reduced the strain on hypoxic pockets by 52% compared to rest.
This study provides insight into cortical oxygen dynamics in awake, behaving animals and at the same time establishes a tool to delineate the importance of oxygen tension in physiological processes and neurological diseases.
