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3 days ago
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The first mapping of mitochondria in the brain has just been revealed. This is yet another step towards understanding these structures which supply their energy to brain cells and are involved in a variety of illnesses, including mitochondrial diseases whose diagnosis has been possible for the past ten years or so.
News of this advance could easily have been ignored by many people, had it not been published in the prestigious journal, Nature1. This first mapping of brain mitochondria has been revealed by a French-American team of scientists, and somewhat overturns previous beliefs.
Mitochondria are little understood by the general public, although they form the basis of all life: these tiny bacteria, which live in symbiosis with and within our cells, supply them with the energy they require to function. “The oxygen we breathe enables them to degrade the nutrients we ingest. Thanks to this process, called oxidative phosphorylation, they supply fuel to all our tissues and organs,” explains Michel Thiebaut de Schotten, joint author of the Nature article and a neuroscientist at the Institute of Neurodegenerative Diseases2 in Bordeaux (southwestern France). “Without mitochondria, there would be no multicellular life.”
The mitochondria in brain cells have become a focus for scientists for a very good reason: the energy needs of our brains are considerable. “It is estimated that the brain consumes 20% of all the energy produced by the body. And yet we had no idea how mitochondria were distributed in this organ, and whether this distribution might throw new light on its functioning,” says Thiebaut de Schotten, a specialist in brain imaging.
A groundbreaking approach
A meeting with his colleagues Martin Picard and Eugene Mosharov, researchers in cell biology and experts in mitochondria at Columbia University in New York (US), gave rise to their ambitious project to combine their two disciplines in order to precisely quantify the brain cell mitochondria in each region of the brain. To achieve this, they developed an entirely new method which consisted in finely measuring the quantity of mitochondria present in a slice of human brain (collected post mortem) and recombining this with the image of a standard brain obtained by functional MRI.
In practice, the brain slice was cut into small, 3 cubic-millimetre pieces in each of which the quantities and specificities of the mitochondria were analysed. All this data was then represented in 3D on an image of the brain. “Each tiny piece had a corresponding one obtained from brain imaging,” says Thiebaut de Schotten, who was then able to build a true predictive mathematical model and extrapolate these results to the entire brain.
“We achieved a very-high resolution map of the distribution of mitochondria in the brain,” he rejoices. “For although the initial pieces were 3 mm on each side, brain imaging can go down to a resolution of 1 cubic millimetre.”
Marked disparities between brain regions
This mapping, which had never been revealed, came as a shock to the two scientists. Although they had suspected differences between brain regions, they had not anticipated such marked heterogeneity. The first surprise was that grey matter, the central part of neurons, concentrates twice as many mitochondria as white matter, which makes up all the connections between neurons.
“We were not expecting such a marked difference,” the researcher comments. For all that, white matter is anything but a series of passive cables. “The mitochondrial density there is nevertheless astonishingly high,” emphasises Picard. “This shows the considerable energy required by connections in the brain.”
The second major finding was that within the grey matter, there were clear disparities between different brain regions. “Those that have appeared more recently during our evolution – notably the frontal and parietal lobes, which are highly developed in humans – contained the highest levels of mitochondria. More ancient regions – such as the olfactory system and hippocampus, which we share with crocodiles – had much lower energy demands,” stresses Thiebaut de Schotten. “During evolution and the appearance of functions such as language, spatialisation or conscience, it seems that the brain has required increasing energy in order to function.”
Diseases linked to the deterioration of mitochondrial activity
This energy mapping of a healthy brain is only a first step for the scientists, who now want to look at conditions connected to mitochondrial dysfunctions, starting with so-called mitochondrial diseases. “Clinically diagnosed only for about a decade, these rare genetic illnesses with a variety of symptoms are related to a mutation affecting the genes responsible for energy production,” says Picard.
The scientists also suspect that a deterioration of mitochondrial activity is linked to neurodegenerative diseases such as Parkinson’s or Alzheimer’s, and also to stroke. “In the longer term, we hope to obtain typical brain maps for all these disorders, so that we can compare this ‘brain signature’ with the MRI scans performed in patients,” Thiebaut de Schotten points out.
“This also provides us with a valuable tool to compile personalised energy assessments,” suggests Picard. “Each individual benefits from a given energy budget that the body uses optimally, by prioritising different functions – digestive after a meal, muscular during physical exertion, etc. In the future, this map may well make it possible to say ‘this is the mitochondrial health of the patient’ and find ways to improve it.” In other words, “There has been much focus on the importance of genes during the past thirty years, but without mitochondria, nothing could function in the body. Energy is life.” ♦
