Advanced Medeical Scientist-Programm 2019

Thema: "Epileptic seizures and synaptic network dysfunctions in autoimmune encephalitis"

Zusammenfassung:
Autoimmune encephalitis (AE) is a new group of neurological disorders with autoantibodies (aAB) against distinct neuronal surface antigens, including ionotropic and metabotropic receptors and synaptic clustering proteins. AE is characterized by rapidly progressive encephalitis or a chronic encephalopathy leading to cognitive dysfunction, confusion, psychotic symptoms and frequent seizures. Here, we aim to investigate the effect of aABs on the neuronal network and the balance of excitation and inhibition as a prerequisite for increased susceptibility to seizures. In a proof-of­concept study we will first evaluate patient GluA2 AMPA receptor autoantibodies as epilepsy is a characteristic feature of this subtype of AE. Therefore, high resolution imaging and neurophysiological methods will be applied to investigate the effect of aABs on neuronal network function in-vitro in primary neurons and ex-vivo in an established mause model of AE. Dysbalance of the excitatory to inhibitory ratio will be determined on the single cell level and by recordings of the synaptic network aiming to explain the underlying pathophysiology of seizures in this subtype of AE. These experimental strategies will then be applied also to further subtypes of AE, e.g. with aABs to LGl1 and GABA receptors. The studies might contribute to development of optimized treatment strategies in controlling epilepsy in these disorders.