How does schizophrenia develop?
People with schizophrenia often suffer from cognitive disorders. These include impairments in self-control, attention and concentration, and memory. Inflammatory reactions in the brain may play a role in the development of these symptoms. A team of scientists has now succeeded for the first time in tracing these mechanisms in living, human cells. The researchers from the NMI Natural and Medical Sciences Institute in Reutlingen used a new method to do this. Together with the University Hospital for Psychiatry and Psychotherapy in Tübingen, they investigated how immune cells from patients with schizophrenia damage nerve cells through inflammatory processes. On the other hand, they were able to show that anti-inflammatory drugs have a positive effect in this process. The causal research helps to better understand and treat schizophrenia. The scientific team recently published their progress in schizophrenia research in the renowned journal Nature Communications Biology.
Schizophrenia occurs in about one percent of the population in the course of life. The disease manifests itself through a variety of different symptoms such as hallucinations, ego disorders, delusions and cognitive disorders. People with schizophrenia often suffer from joylessness, lack of drive, and lack of social contact, and the suicide rate is high. Triggers for the disorder may include environmental factors, social influences, substance abuse, or genetics. Some symptoms are easily treatable, others, especially cognitive disorders, have hardly been researched so far. The reason is that nerve cells are needed for experimental studies. These are located in the brain and cannot simply be taken from living people.
Examination with skin cellsThe research team from Reutlingen and Tübingen has now developed a method to get to the bottom of the causes of schizophrenia without taking nerve cells from living people: Instead, the scientists used skin cells from people suffering from schizophrenia. The skin cells were taken from patients at the University Hospital for Psychiatry and Psychotherapy in Tübingen under the direction of Prof. Dr. Andreas Fallgatter. The team led by Prof. Dr. Hansjürgen Volkmer at the NMI in Reutlingen, then reprogrammed the cells into stem cells. Neurons, i.e. nerve cells, and microglial cells could be differentiated from these stem cells. Microglia are the immune cells of the brain.
It turned out that the microglial cells of diseased individuals are activated and damage neurons through inflammatory processes. "They destroy synapses, suggesting that activated microglia limit the function of neuronal networks and thereby cause cognitive disorders," explains Prof. Dr. Hansjürgen Volkmer of the NMI. "That inflammatory responses might play a role in some schizophrenia sufferers has been known for a few years. Until now, however, there was no way to investigate such mechanisms experimentally. We have now succeeded in doing so."
Anti-inflammatories break vicious circleAt the same time, the researchers found that neurons virtually fire up the microglial cells. Both cell types thus negatively influence each other - a vicious circle. The good news: The activity of the microglia could be reduced by pretreatment with minocycline, an anti-inflammatory drug. That reduced synapse loss. "The results help us better understand the individual causes of schizophrenia. Understanding how a disorder develops is the first step in treating it. With our research, we want to contribute to new therapies for schizophrenia that involve the treatment of inflammatory mechanisms," says Prof. Dr. Andreas Fallgatter of the University Department of Psychiatry and Psychotherapy, Tübingen.
Findings strengthen medical locationThe work was funded by the Forum Gesundheitsstandort Baden-Württemberg. "I am very pleased that an important milestone in medical research has been reached with this collaborative project. I am proud of this," says Prof. Dr. Katja Schenke-Layland, Director of the NMI. "The good cooperation with the University Hospital for Psychiatry and Psychotherapy in Tübingen shows that we have important medical expertise in Baden-Württemberg and can achieve a lot with it. This not only contributes to better treatment options for diseases. It also strengthens the healthcare industry in our region."
The publication "Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction" by Dr. Ricarda Breitmeyer (first author) and Prof. Dr. Hansjürgen Volkmer (responsible author) has been published in Nature Communications Biology 6, 472 (2023). It is available online at https://www.nature.com/articles/s42003-023-04852-9.pdf.
About the NMIThe NMI Natural and Medical Sciences Institute in Reutlingen is a non-university research institution and conducts application-oriented research at the interface of bio- and material sciences. It has a unique, interdisciplinary range of competencies for R&D and services for regional and international companies. The institute addresses both the health care industry and industrial sectors with materials technology and quality-oriented issues such as automotive, mechanical engineering and toolmaking.
The research institute is divided into three business units, which are linked by a common mission statement: The search for technical solutions is always carried out according to the highest scientific standards. In the Pharma and Biotech business area, the NMI supports the development of new drugs using biochemical, molecular and cell biological methods. The Biomedicine and Material Sciences business unit researches and develops future technologies such as personalized medicine and micromedicine for new diagnostic and therapeutic approaches. The service offering for customers focuses on the structuring and functionalization of materials and their surfaces. Analytical questions are answered in the Analytics and Electron Microscopy business unit.
The NMI is known beyond the state borders for its incubator concept for start-ups with a background in bio- and material sciences.
The NMI Natural and Medical Sciences Institute in Reutlingen is supported by the Ministry of Economics, Labor and Tourism of the State of Baden-Württemberg and is a member of the Innovation Alliance Baden-Württemberg, an association of 12 non-university and business-related research institutes.
