Adult hippocampal neurogenesis, Rho kinase inhibition and enhancement of neuronal survival

Abstract

Adult neurogenesis occurs throughout life; however the majority of new neurons do not survive. Enhancing the survival of these new neurons will increase the likelihood that these neurons could return function following injury. Inhibition of Rho kinase is known to increase neurite outgrowth and regeneration. Previous work in our lab has demonstrated a role for Rho kinase inhibition and survival of new born neurons from the sub-ventricular zone. In this study we examined the role of Rho kinase inhibition on hippocampal neurogenesis. Two concentrations of Rho kinase inhibitor Y27632 (20 and 100 p,M) and the proliferative marker EdU were infused in the lateral ventricle for 7 days. Quantification of doublecortin +/EdU + cells on the 7th day showed that cell numbers were not significantly different, suggesting no effect on neuroblast generation. Following infusion of 100 mu M Y27632, the number of newborn NeuN+/EdU + neurons at 35 days in the granular cell layer of the dentate gyrus of the ipsilateral side of the infusion did not display a significant difference; however there was an increase on the contralateral side, suggesting a dose effect. Infusion of a lower dose (20 mu M) of Y27632 resulted in an increase in NeuN+/EdU + cells in the granular cell layer of the ipsilateral side at 35 days. These mice also demonstrated enhanced spatial memory as tested by the Y maze with no significant changes in anxiety or novel object recognition. Rho kinase inhibition enhanced the survival of new born neurons in the dentate gyrus with a specific dosage effect. These results suggest that inhibition of Rho kinase following injury could be beneficial for increasing the survival of new neurons that may aid recovery.