FORNEUROCELL II

BAVARIAN RESEARCH ASSOCIATION FOR ADULT NEURONAL STEM CELLS

Watch me if you can: Optical and MRS imaging of neurogenesis in the adult brain

The preclinical and clinical development of any neurogenesis-based therapeutic approach critically depends on the availability of reliable tools to monitor neurogenesis. Thus far, there are no methods or systems available that image and assess ongoing neurogenesis. In our previous work, we generated transgenic mice that express bioluminescent and fluorescent proteins under control of neuronal precursor cell (NPC)-specific promoter of the human DCX gene. Although these mice are valuable tools since they allow for the visualization of NPCs, they present some system-inherent limitations that need to be overcome in order to be able to monitor subtle modulations in neurogenesis. Thus, the present project aims i) to increase the specificity of the DCX-promoter models by implementing cre-lox technology, and ii) to increase the power of the DCX-promoter models by using of a tri-fusion multimodal reporter construct. Such mice will be of high value for the consortium in any studies that involve time-resolved analysis of neurogenesis and for future neurogenesis-oriented drug-development. A further goal is to develop a neurogenesis-imaging platform applicable in humans. Therefore, the present project aims to use nuclear magnetic resonance spectroscopy (MRS) to identify MRS-bio-markers and spectral signatures that are highly specific for neural stem and progenitor cells and/or that indicate alterations in neurogenesis. We will i) establish a technical platform using a perfusion chamber for NMR tubes that will allow MRS of samples under optimal cell culture conditions. In addition, we will ii) identify cell type specific MRS signatures, and iii) correlate such signatures and composite patterns of signatures with neurogenesis and neurogenesis-associated events.