Disturbed gene activity in the brain as a result of heart problems?
Possible connections between the heart function and the brain have been discussed in the professional world for a long time, but the underlying mechanism has so far remained unclear. A current study now shows that heart problems result in impaired gene activity in the memory center of the brain, which leads to cognitive losses.
Researchers from the German Center for Neurodegenerative Diseases (DZNE), the University Medical Center Göttingen (UMG) and the German Center for Cardiovascular Research (DZHK) looked for possible causes for the connection between cognitive impairments and heart problems in laboratory studies – and they found what they were looking for. The gene activity in the brain is accordingly impaired in the event of cardiac disorders, which leads to cognitive losses. The corresponding study results were published in the specialist magazine “EMBO Molecular Medicine“.
Relationship between the heart and the brain
Last year, a research group from the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) in collaboration with researchers from the Heart Center Leipzig had already proven that a Heart failure also weakens the brain. With impaired heart function, the density of gray matter in the brain decreased.
Four million people affected
“In Germany around four million people are affected by so-called heart failure: their heart muscle is too weak to pump enough blood through the body and is therefore abnormally enlarged,” reports the DZNE in a press release on the current study results. Not only do physical fitness and quality of life suffer as a result, but the people affected also have an increased risk of dementia, the DZNE continues.
Cognitive deficits due to heart failure
“People with cardiological problems, especially heart failure, can experience noticeable cognitive deficits and an increased risk of Alzheimer’s disease. Possible reasons include the impaired blood supply to the brain and disorders of the hippocampus, which is the control center of memory, ”explains Professor André Fischer from the Göttingen University Medical Center.
Impairment of gene activity
So far, however, it has remained completely unclear which malfunctions are triggered in the nerve cells, says Professor Fischer. In the current study, the researchers were able to demonstrate for the first time in mice that an impairment of gene activity in the hippocampus developed as a result of heart problems. In addition, the mice with heart failure did significantly worse in memory tests than their healthy conspecifics, reports Professor Fischer.
Winding the DNA is crucial
When examining the nerve cells from the hippocampus of the mice with cardiac insufficiency, the researchers found increased stress signals and altered gene activity. The latter depends on the changed winding of the DNA. The genetic make-up of a mouse – and also of humans – comprises around 20,000 genes each, of which only a part is active in each cell. However, this is not a simple on or off state, but the activity can be strong or less strong, which depends, among other things, on how tightly the DNA is wrapped and how accessible the genes on it are.
According to the researchers, the DNA of both mice and humans is over a meter long, but in a cell it is strongly compressed. But the “genes can only be active if they are accessible to the machinery of the cell” and “to do this, the DNA has to be wrapped a little loosely at the relevant points,” explains Professor Fischer. This is “similar to a ball of yarn from which loops protrude.”
In mice with heart problems, the DNA in the nerve cells was coiled more tightly than in healthy conspecifics and various genes that are important for the function of the hippocampus were therefore less active than in healthy animals, reports the research team of its study results. The cause of the tight DNA wrapping is said to be chemical changes in the histones, special proteins that function, so to speak, as spools of thread around which the DNA is wrapped.
New therapeutic approaches
In previous studies, the researchers had already looked for active substances that affect the histones and identified the cancer drug “Vorinostat” as an active substance that can alleviate genetic and age-related memory problems in mice. As part of a clinical study by the DZNE, vorinostat is already being investigated for the treatment of people with Alzheimer’s disease.
In the current study, the researchers administered this active ingredient to the mice with cardiac insufficiency, which did not significantly change the heart’s pumping capacity, but improved memory performance. The study not only shows a cause for the increased risk of dementia in people with heart problems, but also points to a possible drug therapy for mental deficits.
“Vorinostat has a proven effect on histones and thus on gene activity. Our study thus provides initial indications of the molecular processes that contribute to cognitive disorders in heart problems and it shows possible starting points for therapy, ”emphasizes Professor Fischer. So far, however, it remains unclear why the gene activity in the hippocampus is disturbed as a result of heart failure.
Important questions that need to be clarified in future studies are, for example, what role the insufficient blood supply to the brain plays and whether substances that affect the histones may be released from the sick heart, summarizes Professor Fischer. (fp)
Author and source information
This text complies with the requirements of specialist medical literature, medical guidelines and current studies and has been checked by medical professionals.
Dipl. Geogr. Fabian Peters
- George Sflomos, Cathrin Brisken, et al.: Intraductal xenografts show lobular carcinoma cells rely on their own extracellular matrix and LOXL1; in: EMBO Molecular Medicine (veröffentlicht 22.02.2021), embopress.org
- German Center for Neurodegenerative Diseases (DZNE): A weak heart is bad for the brain (published 02/26/2021), dzne.de
This article is for general guidance only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor.