Vogt, Johannes | Kepser, Lara-Jane | Endle, Heiko - C 15

Neuronal regeneration in the brain is limited. Therefore, neuronal replacement, i.e. by introduction of immature neurons aiming to replace lost function, is a unmet need in neurodegenerative disorders. Recently, application of IPS or hES cell derived dopaminergic neurons in Parkinson´s disease patients suggested functional integration and improved clinical outcome. However, the molecular mechanisms underlying neuronal survival and integration into brain circuits, a prerequisite for successful regeneration, are by far not understood. 

In the adult brain, neurogenesis and neuronal integration was observed in the hippocampus and was associated with improved cognition. We have previously shown that bioactive lipids like lysophosphatidic acid (LPA), regulate glutamatergic activity and increased the number of adult generated neurons. While our data suggest that neuronal activity and the LPA/LPA2/PRG-1 signaling axis enhance neuronal maturation and circuit integration of immature neurons, the underlying mechanisms are not clear. We therefore aim to characterize the molecular signaling in immature neurons in Prg-1^-/- animals, which display enhanced maturation and increased circuit integration. Using a ribosomal mRNA “trap” mouse line, we aim to specifically target immature neurons and to analyze them by mRNA sequencing. 

Moreover, we will investigate cell death mechanisms of adult generated neurons and the role of bioactive lipids within. Finally, we will analyze integration of adult generated neurons in Prg-1^-/- animals and the ability of physical exercise to increase neuronal integration in these animals.

• Morphological and biochemical characterization of adult generated neurons
• Electrophysiological analysis of network integration of adult generated neurons
• mRNA Seq of adult generated neurons
• Transgenic mouse lines with altered bioactive lipid signaling in the brain
• In-vivo cell death analyses
• Connectome analysis of adult generated neurons in different transgenic mouse lines

• Center for Molecular Medicine Cologne (CMMC)
• Center for Anatomy (UoC)
• CECAD Research Center

• Center of Molecular Medicine Cologne (CMMC)
• Dept. of Molecular and Translational Neuroscience, Institute of Anatomy II, University Hospital of Cologne

• Center of Molecular Medicine Cologne (CMMC)