Glial (patho)physiology

We study the interactions between neurons and glial cells, both in the healthy brain and in the context of neurological diseases. In particular we focus on the white matter disease MLC, a disease characterized by dysfunctional astrocyte water and ion homeostasis leading to chronic white matter oedema. Our team is embedded in both the VU University medical center (Department of Childhood Neurology headed by Prof. Marjo van der Knaap) and the CNCR (Department of Integrative Neurophysiology headed by Prof. Huibert Mansvelder).


Interactions between glia and neurons are crucial for a healthy brain

Electrical activity of neurons in the brain is the basis of all our thoughts and actions. Electrophysiologists have been using intracellular or extracellular electrodes for the last century to understand how these electrical signals generate our thoughts. However, neurons only make up a part of the cells in our brain. The other cells, collectively called Glia (greek for Glue) were long thought to merely fill the gaps and support the neurons. Glia are mostly electrically silent, so electrophysiological studies confirmed the idea that these cells are not doing much.

However, with the advent of life-cell imaging techniques and cell-type specific transgenic approaches, this view is rapidly changing. Research in the last 2 decades has shown that glia actively participate in brain functioning. For example, there is bidirectional communication between neurons and astrocytes changing synaptic transmission. The oligodendrocytes that form the myelin sheath wrapping neuronal axons dynamically adjust their wrapping. And microglia, the brain immune cells, are crucial for clearing away unnecessary connections between neurons.

In our group we focus on the dynamic interactions between neurons and glia. We use a combination of electrophysiology, imaging and transgenic mouse models to investigate how glial function modulates neurotransmission. In particular, we focus on diseases characterized by glial dysfunction.

Astrocytes in brain ion and water homeostasis

Electricity in the brain relies on movement of ions between intracellular and extracellular compartments. Such ion movements are inevitably accompanied by the displacement of water, through osmosis. Since even minor brain swelling can lead to severe brain damage and even death, brain ion and water movement has to be tightly regulated. Astrocytes, important but understudied brain cells, are crucial for this. Dysfunctional astrocytes are the cause of many neurological diseases. We focus on the white-matter disease ‘Megalencephalic Leukoencephalopathy with subcortical Cysts’ (MLC) as a prototype for diseases in which brain ion and water homeostasis is disturbed. We try to understand which proteins play a role in astrocyte homeostasis, and how their dysfunction disturbs neuronal functioning.