How blood vessels sense the metabolic state of neurons

How blood vessels sense the metabolic state of neurons

The brain is our most energy-hungry and metabolically active organ. It is responsible for our thoughts, ideas, movement and ability to learn. Our brain is powered by 600 km of blood vessels that bring it nutrients and remove waste products. However, the brain is also very fragile. The blood vessels in the brain have evolved into a tight protective barrier - the blood-brain barrier - that restricts the movement of molecules in and out of the brain. It is important that the brain can regulate its environment. On the one hand, pathogens or toxins are prevented from entering the brain, and on the other hand, necessary messenger substances or nutrients can pass through them unhindered.

Epigenetics turns on the nutritional program
Because of their close relationship, it is important that the brain and its vessels communicate intensively with each other. Recent work in Asifa Akhtar's laboratory in Freiburg has shown that blood vessels can sense the metabolic state of neighboring nerve cells.

The researchers found that the epigenetic regulator MOF is required to equip neurons with the correct metabolic enzymes needed to process fatty acids. “Something has to tell the nerve cells that there are nutrients and they should turn on the programs necessary to process them,” explains Bilal Sheikh, lead author of the study. “MOF goes to the DNA and turns on the genetic programs that allow cells to process fatty acids in the brain.”

Fatty acids are found in foods and are used to produce energy and build complex lipids needed in cell membranes. When MOF activity is defective, as is the case in neural developmental disorders, neurons cannot process fatty acids. This leads to their accumulation in the spaces between brain cells. In their studies, Asifa Akhtar's team found that this fatty acid imbalance is sensed by the neural blood vessels, stimulating them to mount a stress response by loosening the blood-brain barrier. If the metabolic imbalance persists, the leaky blood-brain barrier can trigger a diseased state.

Collapse of neuronal blood vessels
The study lays the foundation for a better understanding of how nerve cells and blood vessels in the brain talk to each other, and shows how changes in the metabolic environment of one cell type in a complex organ can directly influence the functionality of surrounding cells and thereby influence overall organ function. "Our work shows that proper metabolism in the brain is critical to its health. A defective neural metabolic environment can cause vascular inflammation, dysfunction of the cells that form the blood-brain barrier, and increased permeability. What can follow is a collapse of neural blood vessels," explains Asifa Akhtar. This is particularly important because the breakdown of neuronal blood vessels is a hallmark of the onset of age-related diseases such as Alzheimer's and vascular dementia. Better characterization of the molecular changes that induce vascular dysfunction will help develop better treatments for these debilitating pathologies.