Introduction:

The (pro)renin receptor ((P)RR) is a single-transmembrane domain receptor that is involved in embryonic neuronal development. Since the (P)RR is expressed during specific stages of adult hippocampal neurogenesis we performed functional analyses in mice possessing a dentate gyrus (DG)-specific (P)RR-knockdown.

Methods:

For loss-of-function studies 1 µl of vector concentrate (LV-(P)RR-shRNA vs. control) was stereotactically injected into the DG of young adult mice. Stage specific markers were counted throughout the rostrocaudal extend of the infected granule cell layer. To investigate whether (P)RR-Knockdown affects the maintaince of adult born neurons we birthdated newly born cells by a single BrdU-injection 8 weeks before injecting the lentiviral constructs and counted the total number of BrdU/NeuN/GFP-positive cells per infected area 4 weeks after stereotactic surgery.

Results:

The (P)RR is expressed by doublecortin (DCX)-positive neuroblasts as well as postmitotic neurons (NeuN-positive), but not by Sox2-positive neuronal stem cells. Mice injected with LV-(P)RR-shRNA reveal a marked reduction in the number of DCX-positive neuroblasts per mm² infected area as compared to those injected with the control vector (1916.26±63.18 vs. 877.7±105.99; p<0.001). The number of proliferating cells (pH3-positive) as well as apoptotic cells (caspase3-positive) remained unaffected. Also we found no differences in the total number of BrdU-labelled cells expressing NeuN and the respective shRNA.

Conclusion:

The data identify the (P)RR as a stage specific regulator of adult hippocampal neurogenesis. It appears to be necessary for (1) a proper neuronal cell differentiation and (2) is not required for the survival of neurons after they have fully matured.