Lichtgedanken 05

Rubrik 29 05 | LICHT GEDANKEN Initially, the team of scientists studied nerve cells in cell culture. »Step by step, we could prove how the antibodies cau- se the withdrawal of the AMPA recep- tors with this subunit in the cell. We were able to trigger a chain of compen- sation mechanisms which lead to AMPA receptors without this subunit taking over the signal transmission in the syn- apses«, explains the biologist Dr Holger Haselmann. »With fatal consequences for the functioning and excitability of the synapse.« The next stage saw the researchers induce the disease in an animal model and investigate the nerve cells in the mice’s brain, which had been administered with the antibodies. The same reorganization processes that had occurred to the AMPA receptors in the cell culture were once again recorded. The consequences of this reorganiz- ation also became clear in the animal model. Holger Haselmann: »The abi- lity of the synapses to adapt to the ac- tivity requirements was reduced in the ill mice in comparison with the healthy ones.« Known as »synaptic plastici- ty«, this characteristic is required for networking processes in the brain. Fi- nally, behavioural tests showed that the animals with the disease suffered from limited cognitive performance. By way of comparison: patients with AMPA-receptor-autoimmune encepha- litis suffer from confusion and problems with short-term memory. Revealing the pathophysiology of the rare autoimmune disease The scientists work in Jena and Würz- burg as part of the »ReceptorLight« collaborative research centre are inves- tigating the functioning of receptors using high-end microscopy. High-re- solution fluorescence microscopy can be used to show the AMPA receptors in the synapse region with a resolution of 40 nanometers. »This state-of-the-art imaging technology makes it possible to grapple with and answer clinically relevant questions at a molecular level«, highlights Christian Geis. »We have been able to explain the underlying pa- thophysiology of a rare autoimmune disease.« This allows the scientists to contribute to a faster diagnosis of the autoimmu- ne inflammation of the brain, the sym- ptoms of which are sometimes difficult to classify and and misunderstood oc- casionally. If the disease is suspected, immune tests can be used for a fast di- agnosis. And, once the autoimmune di- sease has been diagnosed, it can mostly be treated successfully, as was the case for Susannah Callahan.  Prof. Dr Christian Geis and Dr Holger Haselmann (in the front). F E AT U E Contact Prof. Dr Christian Geis Clinic for Neurology Am Klinikum 1, D-07747 Jena, Germany Phone: +49 36 41 9-32 34 13 Email: christian.geis@med.uni-jena.de www.neuro.uniklinikum-jena.de Original publication: Human Autoantibodies against the AMPA Receptor Subunit GluA2 Induce Receptor Reorganization [...], Neuron (2018), DOI: 10.1016/j.neuron.2018.07.048 Photo on the left: test subject during an electroencephalogram (EEG). In the case of an encephalitis, changes to the brainwaves can be measured.