Out of Balance Homeo-brain" project explores disruption of brain cell homeostasis

Being in balance – this is also important for the cells in our brain. If their state of equilibrium, or homeostasis, is disturbed, this can be the cause of neurodegenerative diseases in old age, such as Alzheimer’s, other dementias or Parkinson’s disease. In the “Homeo-Brain” project, scientists at the Technische Universität Braunschweig aim to study the homeostasis of brain cells in greater detail and develop new measuring instruments for this purpose. The project is being funded by the state of Lower Saxony and the Volkswagen Foundation with 1.4 million euros from the Volkswagen Foundation’s “Niedersächsisches Vorab” program and will start on April 1 of this year.

The human brain consists of 83 billion nerve cells and just as many glial cells. Their inner milieu is kept in a state of equilibrium by finely tuned metabolic processes, the so-called metabolic homeostasis. One of the main causes of diseases in old age is that the metabolic homeostasis of the brain cells is disturbed. This is where the “Homeo-Brain” project comes in: Scientists want to investigate how the subcompartments of nerve cells – cell bodies, dendrites, axons and synapses – interact with each other and with the glial cells and what effects a disturbed metabolic homeostasis, for example after an infection, has on the brain.

“It is assumed that the compartments of neurons can act independently of each other. But we want to know: What happens when one compartment of a nerve cell is altered? How does that affect the other compartments? For example, if we allow a drug or interaction with a brain immune cell to affect only the axons, does that also change the dendrites, the cell body, and the synapses? Might it even change the entire functionality and structure of a neuron? And how does it change the interaction of glial cells with neurons?” said the project’s spokesperson, Professor Martin Korte, head of the Department of Cellular Neurobiology at TU Braunschweig.

Interdisciplinary approach for new measuring instruments

In order to observe such processes in living neurons, precise measuring instruments have been lacking until now. The research team now wants to develop these in the interdisciplinary project. To this end, researchers from neurobiology, systems biology, chemistry and engineering sciences such as mechanical and electrical engineering are working together. Among other things, a new type of flow chamber paired with tiny nano-LED modules is to be created that will make it possible to study living nerve cells over a longer period of time. The flow chamber will be used to precisely regulate the substances or pathogens with which individual compartments of nerve cells come into contact. The nano-LED modules act as small microscopes and allow for permanent observation. For example, it is possible to observe over several weeks how nerve cells and their compartments change as a result of exposure to viruses or bacteria, or what long-term effects active substances have on nerve cells.

In doing so, the project links three research centers of the TU Braunschweig – the Braunschweig Center for Systems Biology (BRICS), the Center for Pharmaceutical Process Engineering (PVZ) and the Laboratory for Emerging Nanometrology (LENA) – in their research activities in the core research area “Infection and Therapeutics”. Also involved in the project are the Helmholtz Centre for Infection Research (HZI), the Max Planck Institute for Experimental Medicine and the University of Lübeck.

“With this cross-disciplinary collaboration, we want to contribute to a better understanding of disease processes in the brain and enable targeted research into the causes of neurological diseases that often occur in old age. More precise knowledge of metabolic homeostasis can also help test active substances more efficiently,” says Professor Martin Korte, neurobiologist at TU Braunschweig and head of the “Neuroinflammation and Neurodegeneration” working group at the HZI. “With this project, we want to lay the foundation stones to enable basic research to advance the fight against important brain diseases in terms of measurement and therapy. We see ourselves here as bridge builders between disciplines, but also between methodological development and its biomedical application.”