At the Institute for Pharmacology and Toxicology, one of the main interests in our research group, led by Prof. Daniela C. Dieterich, is the interaction of neurons and astrocytes in synaptic function, plasticity and aging. Neurons and glial cells form an effective cellular communication network by means of trillions of synapses and together maintain and shape synaptic function but also a failure of supportive actions by glial cells can contribute to pathological synaptic dysfunctions in disease and aging processes. We want to identify and elucidate molecular mechanisms involved in astrocytic support of neurons and synaptic function in several contexts such as synaptic plasticity and learning as well a regional variation and we want to understand how these mechanisms might be altered in healthy aging and thereby contribute to aging processes and of course, we want to find ways to pharmacologically manipulate these mechanisms to support healthy aging and rejuvenate synaptic function.
For that, we focus on the molecular and systemic characterization of neuronal and astroglial proteomes in the hippocampal and cortical system in rodents. We use an interdisciplinary spectrum of methods from proteomics, fluorescence microscopy, molecular biology and bioinformatics. The central experimental tool of our investigations is the metabolic labeling of de novo synthesized proteins by means of functionalized molecular building blocks, such as azide and alkyne amino acids or azido derivatives of L-fucose. These bioorthogonal functional groups can be labelled by [3+2] azide-alkyne cycloaddition („click chemistry“) with either a fluorescent group or a biotin residue and subsequently visualized or specifically purified and identified. The two techniques BONCAT and FUNCAT allow the specific and time-resolved identification and in situ visualization of newly synthesized endogenous proteins.
As part of SynAGE, we especially focus on how increased tissue stiffness of the aging brain affects astrocytic signaling cascades, changes astrocytic physiology and astrocytic influences on neuronal synaptic signaling and how anti-aging treatment is able to influence these processes.