Effect of doublecortin-like (DCL) manipulations on hippocampal neurogenesis in the adult mouse; functional implications

Researcher: 
Dirk Jan Saaltink
Effect of doublecortin-like manipulations on hippocampal neurogenesis
Effect of doublecortin-like manipulations on hippocampal neurogenesis

Adult neurogenesis is a brain process in which new neurons are born from neuronal stem cells and develop into mature neurons which integrate into the existing network. Adult neurogenesis takes place in both bulbus olfactorius and the hippocampus of adult animals.

The hippocampus is primary related to learning and memory and includes a large population of gluccocorticoid and melanocorticoid receptors. Both receptors play an important role in the HPA axis which is activated when an organism perceives a stressor. Severe and chronic stress decrease neurogenesis and anti-depressive drugs need neurogenesis to function properly. However, the precise function of adult neurogenesis is unknown. In the past, no models were available to manipulate neurogenesis specifically. The aim of this project is the validation of a new mouse model in which RNA interference is used to knock down a protein which plays a crucial role in adult neurogenesis. We target the Doublecortin-like kinase 1 (DCLK1) splice variants DCL and CARP to investigate their role in adult neurogenesis. As the name already suggests, doublecortin-like shows a high homology with doublecortin which plays an important role in the migration and maturation of new born neurons.

By studying this process we hope to find new targets for depression and stress related diseases but also epilepsy patients might profit from this research model.

06/07/2009