Despite the enormous impact of major depression, currently available antidepressants are far from being satisfactory. This symposium will point out highly innovative strategies for the development of novel treatment targets.
Claus Normann (Freiburg) will give an overview of the neuroplasticity hypothesis of depression, showing data ranging from hippocampal brain slices to behavioural experiments in rodents and its translation to humans. He will describe the molecular mechanisms of synaptic long-term plasticity that regulate the strength of synaptic transmission in response to environmental stimuli.
Stefan Vestring (Freiburg) will go further into the modulation of plasticity in the mechanism of action of ketamine. He will present data on the role of excitation-inhibition balance and focuses on the specific inhibition of inhibitory GABAergic interneurons via antagonism of the NMDAR subunit GluN2D on interneurons by small molecules and siRNA-based strategies.
Tsvetan Serchov (Strasbourg) investigates the synaptic protein Homer1a-mediated modulation of metabotropic glutamate receptor 5 (mGluR5) signalling and AMPA receptor function as mechanism mediating the rapid antidepressant effects of ketamine and sleep deprivation. His data demonstrate a pronounced therapeutic potential of in-vivo application of different cell-membrane permeable TAT-fused peptides, which might provide a novel strategy for rapid and effective antidepressant treatment.
Gerhard Schratt (Zürich) identified a microRNA cluster (miR379-410) whose deletion results in hypersociability and stress resilience in mice. Rescue experiments identified individual miRNAs, which are causally involved in the behavioural and molecular phenotypes, including the plasticity-regulating miR-134. In the future, local or systemic delivery of anti-miRs in mice will be explored as a novel strategy to promote stress resilience as a first step towards the development of miRNA-based antidepressant treatments.