The workgroup Cellular Neurobiology and Neuro-Nanotechnology of the Dept. of Biological Sciences, University of Limerick (formerly WG Molecular Analysis of Synaptopathies, Ulm University) is interested in the underlying components able to modify synaptic plasticity and transmission in the Central Nervous System (CNS) in health and disease. Thereby, synaptopathy defines key features of neurodegener
ative and psychiatric diseases. It implies that disruptions in synaptic structure and function are potentially the major determinant of such brain diseases. Using a combination of biochemical, cellular, molecular and behavioral approaches, we investigate proteins of excitatory postsynapses focusing on their deregulation in neurodevelopmental and neuropsychiatric disorders such as Autism Spectrum Disorders, Alzheimer’s disease and Schizophrenia. We are especially interested in the functional interaction of biometals and synaptic proteins in mechanisms such as synapse formation and maturation in health and disease. Given that dysregulation of trace metals is reported in many brain disorders, their role in the modification of synaptic function needs to be investigated in more detail. Especially since many brain disorders seem to not only have a genetic but also an environmental component triggering the disease. To investigate the role of biometals in disorders of the CNS, we use several approaches. For example, targeted manipulation of biometal levels in animal models and cells derived from human induced pluripotent stem cells is a major goal in our research. Nanoparticles) and assays designed to evaluate their potency to influence synapse formation, maturation and plasticity has become an important part of our research. On the other hand, we investigate human patients with selected disorders and perform a state of the art assessment of their trace metal status and clinical phenotype to define subgroups with biometal abnormalities, which can be associated with specific clinical presentations. Understanding how environmental and genetic factors contribute to synaptic function will hopefully allow the development of research strategies to normalize function in individuals with synaptopathies.
