Modulators of neurogenesis

1. Transforming Growth Factors as modulator of neurogenesis

Sebastien Couillard-Despres, Mahesh Kandasamy, Sridhar Chirasani, Ludwig Aigner

Neurogenesis is reduced in a number of neurodegenerative diseases. The cytokine
TGF-beta might be one of the molecular candidates involved in the reduced neurogenesis. TGF-beta is elevated in a number of CNS diseases and inhibits neural stem cell proliferation in the brain. Our future goal is to identify the molecular mechanisms underlying the TGF-beta induced inhibition of neurogenesis, to identify the diseases where TGF-beta is involved in the inhibition of neurogenesis and to develop therapeutic strategies based on the TGF-beta1 mechanisms.


Figure 2: TGF-beta Inhibits Neurogenesis in the Adult Brain


2. Ageing- and stress-associated molecules and their impact on neurogenesis

Sebastien Couillard-Despres, Katrin Wagner, Ludwig Aigner

Ageing and stress are factors that impair neurogenesis. We are investigating the molecular mechanisms underlying these effects. Recently, we found that ageing abolishes the pro-neurogenic effects of the anti-depressant drug fluoxetine.


Figure 3: Modulation of Neurogenesis

3. Identification of molecular mechanisms that promote neuronal differentiation

Katrin Wagner, Ludwig Aigner, Sebastien Couillard-Despres.

We have identified doublecortin (DCX) as a gene that is specifically expressed in neuronal precursors and in young immature neurons. Moreover, we were able to identify and to clone the DCX promoter. Currently, we are investigating regulation of DCX gene expression in order to identify mechanisms that promote neuronal differentiation.


Figure 4: Expression of DCX in Neurogenesis


Mesenchymal stem cells and their impact on neurogenesis

Francisco Rivera, Carolin Steffenhagen, Ludwig Aigner

The use of adult neural stem cells in the therapy of demyelination diseases or for axonal regeneration is limited by their low oligodendrogenic differentiation. Along the course of investigations on the influence of different stem cell populations, we found that mesenchymal stem cells instruct oligodendrogenic fate on neural stem cells. The future goal is the identification of this activity and to use mesenchymal stem cells in experimental and clinical therapies for de-myelinating diseases.


Figure 5: Oligodendrocyte in vitro

Imaging of neurogenesis

1. Optical imaging of neurogenesis

Sebastien Couillard-Despres, Ludwig Aigner

We have developed cell lines and transgenic mice that allow optical imaging of neurogenesis. The tools are based on the expression of fluorescent or bioluminescent proteins under the control of the neuronal precursor specific promoter of the DCX gene.


Figure 6: Bioluminescent Imaging of Neurogenesis in the Postnatal DCX-Luciferase Mouse

2. MR spectroscopy of stem cells and of neurogenesis

Paul Ramm, Sebastien Couillard-Despres, Ludwig Aigner

Currently, there is no technology or method available to detect neural stem cells and neurogenesis in humans in vivo. MR spectroscopy might provide the basis of such a method. We are currently exploring the possibility of using MR spectroscopy to identify stem cell specific characteristics and have investigated a 1,28 ppm MR signal.

Retinal stem and progenitor cells and retinogenesis

Ludwig Aigner

Despite the presence of stem and progenitor cells in the adult eye, the retina lacksthe capacity for cellular regeneration. To analyze this in more detail, we identified and characterized retinal stem and progenitor populations. The future goal is to modulate proliferation and differentiation of these cells with the goal to promote retinal regeneration.


Figure 7: Various Cell Populations in the Eye are Putative Retinal Stem Cells