Dialogue between brain and gut: Signals from the gut are known to be able to influence our brain. But the “conversation” apparently also works the other way around, as a study reveals. Accordingly, cells also migrate from the brain to the intestines and sometimes bring harmful substances with them. This could explain why some neurological diseases such as Parkinson’s are also accompanied by changes in the intestines.
Our body regulates a wide variety of processes via the so-called gut-brain axis. Processes in our intestines can not only have a local impact on digestion, metabolism and intestinal flora, but also via the brain on our mental health and nervous system. Many neurological diseases such as Parkinson’s, multiple sclerosis and depression are linked to inflammation in the intestines, as previous studies show. It is also known that immune cells from the intestine or substances produced by intestinal microbes often migrate to the brain.
Proteins from the brain also in the intestines
A team led by Rhonda McFleder from the Würzburg University Hospital has now investigated whether this communication also works in the opposite direction – from the brain to the intestine. To do this, the neurobiologist and her colleagues used mice with Parkinson’s-like symptoms in the brain and analyzed whether and which substances of neuronal origin were found in the animals’ intestines.
They discovered that alpha-synuclein proteins could also be detected in the small intestines of the mice. These misfolded proteins are considered a key symptom of Parkinson’s disease and accumulate in the brain of those affected, clump together and trigger the death of brain cells. The detection of the alpha-synuclein protein in the mouse intestine fits with previous studies in which this protein was also found in the intestines of human Parkinson’s patients – even before they showed neurological symptoms.
The detection of Parkinson’s-typical proteins in the intestine suggests that the α-synuclein proteins accumulate in nerve cells in both organs and can cause disorders there.
How do the proteins get into macrophages?
Interestingly, McFleder and her colleagues found the alpha-synuclein accumulations not in the intestinal nerves, but in the macrophages of the mouse intestine. But how did the neuronal proteins get into these phagocytes of the immune system? To find out, the scientists sequenced the RNA of the macrophages in various organs of the mice. This gave them information about the type and function of the immune cells.
The comparison showed that the same type of macrophages were found in the brain and small intestine. In both cases these were CD11c+ cells, which have a similar metabolism to certain neurons and can therefore take over alpha-synuclein proteins from nerve cells. However, this type of macrophage was missing in other immune organs such as the spleen, as the researchers report.
Not a one-way street
However, this does not prove that transport really works in both directions. “In order to clearly test whether macrophages migrate from the brain to the intestine, we have developed a method with which we can mark cells in the brain and track their migration to other organs,” says McFleder, describing her team’s further approach. They used a green fluorescent protein label that turned red after being stimulated by light.
The finding demonstrated: “Cells can actually migrate from the brain to the intestine. “The communication between the brain and the intestine is not a one-way street,” explains McFleder. “Our results also suggest that this unique communication is involved in the spread of Parkinson’s disease.”
Findings could be transferable to other diseases
But the macrophage migration observed not only applied to the mice with Parkinson’s, but also to the control group. In these cases, however, the phagocytes had no alpha-synuclein proteins on board. “We have seen that macrophages migrate from the brain to the intestine not only in Parkinson’s but also under control conditions. This gives the findings broader relevance for other neurological diseases,” explains senior author Chi Wang Ip from the University Hospital of Würzburg. “Just as these cells drive pathology in Parkinson’s disease, they could also drive proliferation in other neurological diseases,” he suspects.
In further studies, McFleder and her team now want to examine the migrating immune cells in more detail and identify the molecules that the macrophages specifically direct into the intestine. “We can then develop drugs that block these molecules and hopefully halt the progression of Parkinson’s and other neurological diseases,” says McFleder. (Nature Communications, 2023; doi: 10.1038/s41467-023-43224-z)
Source: Würzburg University Hospital
December 20, 2023 – Claudia Krapp