Abt. Zelluläre Neurobiologie
Tel.: +49 (0)531 391 3225
1.) Nogo-A has been shown to restrict both functional and structural plasticity in the mature brain. Using both in vitro and in vivo approaches we analyze the cellular and molecular mechanisms underlying its activity. Specifically, we study the ability of Nogo-A to regulate the dynamics of the actin cytoskeleton to control structural plasticity at dendritic spines at a fast time scale. Moreover, we use single particle tracing methods to analyze the role of Nogo-A in modulating receptor trafficking at synapses and thus synaptic strength. Finally, we use several behavioral approaches to assess the role of Nogo-A in regulating learning and memory processes.
2.) Brain derived neurotrophic factor (BDNF) signaling via its receptor TrkB is required for structural and functional plasticity. Moreover, aberrant BDNF/TrkB levels are associated with disorders including neurodevelopmental and neurodegenerative diseases suggesting its potential relevance in their therapy. We use in vitro and in vitro approaches to test drugs acting on the endogenous signaling pathways to either modulate the levels of endogenous BDNF (Fingolimod) or to activate TrkB receptor signaling (TrkB agonist antibodies). Our first aim is to analyze their effect in promoting neuronal plasticity and learning under physiological conditions. Moreover, we test the possibility of rescuing the neuronal phenotypes observed in one prototypical neurodevelopmental disorder, Rett syndrome and one neurodegenerative disorder, Alzheimer disease.
3.) Alzheimer disease is characterized by extracellular accumulation of amyloid β (Aβ) peptides and synaptic pathology accompanying the progressive cognitive impairment. Application of soluble Aβ peptides impairs long-term potentiation (LTP), strengthens long-term depression (LTD), and induces a significant loss of synapses and dendritic spines in the hippocampus. The p75NTR neurotrophin receptor specifically binds Aβ and has been shown to modulate both the plasticity and the structure of neurons under physiological conditions. Here we analyze, both in vitro and in vivo whether and by which mechanisms p75NTR might be involved in mediating the Aβ-induced negative effects on synaptic function and structure during the early phases of Alzheimer’s disease.