About a third of people with heart disease suffer from sleep problems. In an article published in the magazine Science shows a team from the Technical University of Munich (TUM) indicate that heart disease affects the production of the sleep hormone melatonin in the pineal gland. The connection between the two organs is a ganglion in the neck. The research shows a hitherto unknown role of the ganglia and points to possible treatments.
Heart disease affects the production of the sleep hormone melatonin by damaging the connections between the heart and pineal gland. This damage is caused by inflammation in the neck ganglia that act as switchboards between the two organs. The findings suggest an opportunity for new drugs to treat sleep disorders in heart patients treatable by targeting the nerve nodes.
It has long been known that melatonin levels can drop in patients with heart muscle disorders, for example after a heart attack. This is generally seen as an example of how heart disease affects the entire body systemically. A team that collaborates with Stefan Engelhardtprofessor of pharmacology and toxicology at TUM, and first author Dr. Karin Zieglerhas now shown that there is a direct cause for sleep disturbances in people suffering from heart disease.
Ganglia as electrical control boxes
“In our work we show that the problems with the heart muscle affect an organ that at first glance seems to have no direct connection with it,” says Stefan Engelhardt in a press release of the TUM. Melatonin is produced in the pineal gland in the brain. Like the heart, it is controlled by the autonomic nervous system, which controls involuntary processes in the body. The associated nerves come from the ganglia, among others. The superior cervical ganglion is especially important for the heart and pineal gland, which contains cells that control both organs.
“To get a good idea of our results, imagine the ganglion as an electrical switch box. In a patient suffering from sleep disturbances due to heart disease, you can think of a problem with one wire that causes a fire to break out in the control box and then spread to another wire,” says Stefan Engelhart.
Nerve connection to pineal gland destroyed
The team found that macrophages – cells that eat dead cells – accumulate in the cervical ganglion of mice with heart disease. The exact mechanisms behind this are still unknown. The macrophages cause inflammation and scarring in the ganglion and the destruction of nerve cells. In mice, as in humans, long fibers from these nerve cells, called axons, run to the pineal gland. At an advanced stage of the disease, there was a significant decrease in axons connecting the gland to the nervous system. There was less melatonin in the animals’ bodies and their day/night rhythm was disturbed.
Similar organic effects were seen in humans. The team examined the pineal glands of nine heart patients. Compared to the control group, significantly fewer axons were found. As in the mice, the superior cervical ganglion in the people with heart disease showed scar tissue and was visibly enlarged.
Stefan Engelhardt, Professor of Pharmacology and Toxicology © Andreas Heddergott / TUM
Starting point for new medicines
The researchers assume that the negative effects of the dead axons become permanent in an advanced stage. “In an early stage, we were able to return melatonin production in mice to its original level by using drugs to destroy the macrophages in the superior cervical ganglion,” says Karin Ziegler. “First, this demonstrates the role of the ganglion in this phenomenon. And secondly, it gives hope that we can develop medicines to prevent irreparable sleep disturbances in heart disease.” That is one of the tasks that the team wants to focus on in the coming years.
Examining ganglia for other possible connections
In addition to new hope for a large number of heart patients that a treatment for sleep disorders will be found, Stefan Engelhardt sees the research as a reason to look at the ganglia from a new point of view. “New methods such as spatial single-cell sequencing make it possible to examine individual nerve cells much more precisely. Our study could lead researchers to systematically look for links between other diseases in organs connected through ganglia that act as switchboards and to look at ganglia as a starting point in the search for new drugs.”
Engelhardt believes that ganglia may also become important from a diagnostic point of view. Because all of the neck ganglia in the heart patients they studied were significantly enlarged, the researchers believe this may indicate heart failure. The size of the ganglia can be easily checked with a conventional ultrasound machine. If the results are confirmed in further investigations, it may be advisable to have more extensive checks of the heart if the ganglia are found to be enlarged.
2023-08-06 09:38:00
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