Our laboratory contributes to this consortium with the long-standing expertise in research on mechanisms of cellular stress in model systems of neurological disorders, including neurodegenerative diseases, acute brain injuries, and epilepsy. The major focus of our work is on intracellular stress pathways featuring mitochondrial dysfunction and apoptotic death pathways triggered by excitotoxicity, oxidative stress and oxygen-glucose deprivation of neurons. Further, we investigate intercellular stress responses that involve neuroinflammatory responses and interactions between microglial cells, astrocytes and neurons. These investigations are performed in model systems of neurological diseases in cultured neurons, glial cell cultures and model systems of neurodegeneration and acute brain injuries in vivo. In these model systems we aim at identifying novel targets mediating neuronal dysfunction and death for the development of therapeutic strategies, including the development and application of small molecule drugs and genetic approaches such as viral and non-viral transfer of siRNA, miRNA, or cDNA. In the cell culture systems and in brain tissue from the in vivo models, we apply biochemical analysis, molecular biological methods and immunocytochemistry combined with (in vivo) fluorescence microscope imaging. Further, we investigate putative therapeutic targets at the functional level by electrophysiology for ion channels, functional parameters of mitochondrial function, parameters of ER-stress and measurements of the calcium homeostasis at the cellular and subcellular level. In particular, we have expertise in investigation of K-channel activities and alterations of the intracellular calcium concentration. Mitochondrial function is assessed at the level of mitochondrial morphology, mitochondrial membrane potential, mitochondrial production of reactive oxygen species and ATP, mitochondrial calcium uptake, and mitochondrial respiration as well as the detrimental release of mitochondrial proteins into the cytosol. We modify mitochondrial function by pharmacological agents and, in particular, by genetic expression systems targeted to mitochondria.

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