Is the cause of diseases such as Alzheimer‘s, epilepsy and schizophrenia rooted in a deficiency or rise in chemical messengers? The „Functional Cell Biology" working group at the Charité University Hospital‘s Institute for Integrative Neuroanatomy in Berlin is looking into this and similar issues. The results are forming the basis of a fundamental understanding of the diseases and are intended to provide indications for therapeutic approaches. Researchers are employing the latest imaging and image analysis techniques and methods in the course of their investigations.

„Functional Cell Biology" Working Group

As Professor of the Centre for Anatomy at the Charité‘s Institute for Integrative Neuroanatomy, Dr. Gudrun Ahnert-Hilger leads the „Functional Cell Biology" working group, where her colleague Dr. Johannes-Friedrich Zander works. One of the research projects currently being worked on by Dr. Ahnert-Hilger and Dr. Zander is looking at the area of the brain which deals with memory, the hippocampus. „Our work is intended to contribute to a better understanding of the causes of epilepsy or Alzheimer‘s", says Dr. Zander, explaining the objective of the research project. This is because „in pathophysiological terms, the hippocampus plays a key role in the development of these diseases." The hippocampus is the area of the brain which, among other things, deals with the consolidation of memory. „In the hippocampus, memory content is transferred from the short-term to the long-term memory", says Dr. Zander. We now know that the central nervous system (CNS) is not a static organ, but is permanently changing as a function of activity and experience. „In this connection, the hippocampus is viewed as a ‚module for explicit memory‘", continues Dr. Zander - this means that patients with bilateral damage to the hippocampus are incapable of learning new facts and events.

The Focus of Interest: Mossy Fiber Synapses

Microscopic and functional differences divide the hippocampus into two corresponding areas called the dentate gyrus and the cornu ammonis. The cells of the dentate gyrus and the cornu ammonis communicate via synapses.

Synapses are specialized links in the brain which allow communication between individual nerve cells, the neurons. „Each synapse has special anatomical characteristics. One of the hippocampal synapse types is extraordinary in its extension and referred to as a mossy fiber synapse", says Dr. Zander. „This synapse is involved in an important processing step in the hippocampal circuit, though its precise function has not yet been fully understood. That is why we are particularly interested in it", he continues.

It is the particular properties of mossy fiber synapses, such as their synaptic strength, synaptic facilitation and their strategic position in the hippocampus which make them so interesting to scientists. There is much to indicate that „mossy fiber synapses are responsible for a wide variety of processes in the brain", says Dr. Zander, adding that scientists are attempting gradually to get to the bottom of this.

Communication in the Cells

Information between the cells in the synapses is actually exchanged by means of neurotransmitters. These are biochemical messengers which pass on, amplify or modulate electrical stimuli from one nerve cell to another nerve cell or other cell. The „Functional Cell Biology" working group is interested in two main neurotransmitters: GABA, short for gamma-amino butyric acid, and glutamate.

„The development and function of the human brain depends essentially on the availability of gamma-amino butyric acid (GABA), an important neural messenger in the central nervous system", explains Dr. Zander. Diseases such as epilepsy and schizophrenia are directly linked to a deficiency of the GABA neurotransmitter. The glutamate messenger is also very importance. In healthy people, glutamate is responsible for memory performance, learning ability and concentration. It has now been scientifically proven that the concentration of this substance is higher in Alzheimer‘s patients and that this leads to continuous stimulation of nerve cells.

Dr. Zander and Dr. Münster-Wandowski, his colleague establishing the post-immunogold labelling technique in the lab and are using modern technology to get to the bottom of the transport mechanisms of vesicular glutamate and vesicular GABA. „Among other things, our research work consequently makes use of electron microscopes equipped with modern digital recording and analysis software", says Dr. Zander.

Gold Labels as Signposts

Dr. Zander‘s working group has come to appreciate above all the versatile potential of digital image evaluation. „We employ image analysis methods to evaluate gold particle labels of the vesicular glutamate transporters (VGLUT)1/2 and of the vesicular GABA transporter (VGAT) in relation to the surface area of the hippocampal mossy fiber (MF) terminals", is how Dr. Zander describes the method used.