Measuring Gene Expression Changes in the Brain as a Result of Heart Failure

Heart failure causes harm to the brain by reducing the supply of blood, and thus the supply vital nutrients and oxygen, to brain cells. The precise details of how this leads to cognitive decline are yet to be fully mapped. Researchers here assess changes in gene expression the brains of mice suffering from heart failure, as a starting point for further investigation of specific mechanisms. The best path forward for this class of contribution to neurodegenerative conditions is to prevent or reverse vascular aging, which has numerous components. There is the narrowing of blood vessels via atherosclerosis; the failure of smooth muscle tissue to appropriately contract and dilate blood vessels, due to cellular senescence, chronic inflammation, and other mechanisms of aging; stiffening of blood vessels via cross-linking in the extracellular matrix; and so forth.

In heart failure, the heart muscle is too weak to pump enough blood through the body and is therefore abnormally enlarged. Physical fitness and quality of life suffer as a result. Moreover, affected individuals have an increased risk of developing dementia. "People with cardiological problems and heart failure in particular may experience noticeable cognitive deficits and increased risk of developing Alzheimer's disease. Possible reasons include impaired blood supply to the brain and dysfunction of the hippocampus, which is the memory's control center. Yet, there is a lack of therapies to effectively treat cognitive deficits in people with heart problems. This is because it is completely unclear which deficiencies are triggered in neurons. There was no data on this so far."

Researchers observed in mice that impaired gene activity developed in the hippocampus as a result of heart problems. "In memory tests, mice with heart failure performed significantly worse than their healthy mates. We then examined the neurons of the hippocampus. In the mice with heart failure, we found increased cellular stress pathways and altered gene activity in neurons."

The genome of a mouse - and also of humans - comprises around 20,000 genes. In any given cell, however, only a part of them is active, switched on, so to speak. This is not a mere on or off state: the activity can be strong or less strong. This depends, among other things, on how tightly the DNA of the genome is wound and how accessible the genes on it are. In both mice and humans, the DNA is more than a meter long. But in a cell, the molecule is so tightly packed that it fits into the nucleus. "Genes can only be active if they are accessible to the cell's machinery. To this end, the DNA needs to be wound a little more loosely at the relevant sites. This is similar to a ball of yarn with loops sticking out of it." In the current study, the DNA was found to be more tightly wound in neurons of mice with heart problems than in healthy mates. Various genes important for hippocampal function were therefore less active than in healthy mice.

Link: https://www.dzne.de/en/news/press-releases/press/a-weak-heart-is-bad-for-the-brain/

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