Millions in funding for mapping molecular changes in brain associated with brain disorders

The Institute for Chemical Neuroscience (iCNS) has been awarded a 23.23 million euro Gravitation grant. The funding will support research aimed at mapping changes in the brain, down to the smallest level, associated with psychiatric symptoms. Utrecht University professor Maarten Kole is one of the applicants of the project, which is a collaboration between universities, university medical centers, and the Netherlands Institute for Neuroscience. The overarching objective of the research is to improve the diagnosis and treatment of neuropsychiatric disorders such as depression, frontotemporal dementia, and anxiety disorders.

In our society, one in four people suffer from a brain disorder. “For many brain disorders, little is known about the molecular mechanisms underlying them,” says consortium leader Inge Huitinga, professor by special appointment of Neuroimmunology at the UvA and head of the Neuroimmunology research group of the Netherlands Institute for Neuroscience. “The relationship between changes in brain tissue and patients’ symptoms is very complex. We do not really know which types of cells, which brain networks and which molecular processes cause the psychiatric symptoms of patients with a brain disease.”

Changes in cells

Maarten Kole, who is also group leader at the Netherlands Institute for Neuroscience, has long been studying the role of glial cells: cells in our brains that, among other functions, provide support for nerve cells.

Kole: “We believe that psychiatric symptoms are related to changes occurring in individual cells, and particularly between the glial cells and nerve cells. There is an increasing amount of brain material available from individuals with psychiatric disorders for investigating this issue. Meanwhile, in chemistry and molecular biology, various promising techniques have emerged, which could fundamentally change research into the human brain.”

The goal is to develop biomarkers, measurable indicators, for the diagnosis, prognosis, and ultimately treatment of the brain disorders that affect many people.

Pooling forces

The researchers hope to ultimately gain more clarity on what exactly happens in the cells and bring this together into a molecular ‘brain atlas’. Various disciplines, including neurobiology, chemistry, data science, and psychiatry, will pool forces to achieve this.

Kole: “The goal is to develop biomarkers, measurable indicators, for the diagnosis, prognosis, and ultimately treatment of the brain disorders that affect many people. If we better understand what exactly goes wrong in the brain, eventually we will be able to measure it in the blood or with PET scans to determine what is happening. This can lead us towards a more personalized approach.”

Human brain material

In contrast to traditional brain research, the researchers in iCNS take human brain material from the Netherlands Brain Bank (NHB) as a starting point. This material comes from individuals who have donated their bodies to science posthumously. Anonymized clinical and genetical information is available for many of these people. The researchers are also collecting cerebral fluid and plasma from living patients with a brain disorder.

Sixteen brain regions

The molecular brain atlas will be created by mapping in great detail the changes occurring in sixteen brain regions known to play a role in neuropsychiatric disorders. Using new computer approaches called machine learning models, the researchers aim to link the large amounts of data being collected to the psychiatric symptoms of approximately 3,000 donors. Subsequently, the researchers will utilize innovative chemical methods to explore how to influence or rectify changes associated with specific symptoms in model systems, such as lab-grown mini-organs made of brain tissue.

Huitinga concludes: “This large-scale and interdisciplinary approach of the new Institute for Chemical Neuroscience has the potential to lead to groundbreaking insights, which are much needed.”