Corresponding increase in mushroom spines in these dendrites is not clear, it might represent a homeostatic mechanism to compensate for the reduction of the learning spines. The functional implications of the observed radiation effects on dendritic spines at the two hippocampal sub regions are not yet clear. Additionally, if or how these radiation-induced alterations may relate to the behavioral, cellular and Arc changes observed at the same dose and/or time used here, remains to be determined. In conclusion, to the best of our knowledge the present report provides the first evidence that in young adult mice, cranial irradiation causes alteration in spine density and morphology in the hippocampus in a time dependent and region specific manner. Since loss of dendritic spines or structural reorganizations of spines play an important role in learning and memory, the observed changes suggest a disruption of neural circuitry that might play a role in radiation induced cognitive impairment. Focal brain ischemia stimulates the proliferation of neuronal precursor cells in the subventricular zone, followed by migration of neuroblasts into the ischemic regions. However, although many neuroblasts reach the injured striatum, very few differentiate into mature neurons. Given that increased neurogenesis around ischemic lesions improves clinical outcome, these findings raise the possibility that enhancing neuronal differentiation and survival could serve as a therapeutic approach to stroke. For an outside factor to support long-term neuronal regeneration, its continuous or repeated administration is necessary. The administration of any therapeutic protein is problematic because it almost never passes the blood-brain barrier and the half-life is relatively short. Gene therapy may be a good alternative, as a single injection is sufficient for local production of the relevant protein for a long period. Wnt proteins are extracellular factors that play important roles in the developed and mature central nervous system. They regulate the proliferation of neural OTX015 202590-98-5 progenitor cells and their differentiation to neurons in the subventricular and subgranular zones. Moreover, the Wnt signaling pathway is an obligate component of neural progenitor cell differentiation into neurons. However, whether Wnt signaling can create the appropriate environment for neuronal differentiation and survival outside the classic neurogenic niche remains unclear, as does its potential contribution to clinical improvement after ischemic injury. The aim of the present study was to investigate the effect of lentiviral-mediated Wnt3a gene transfer on neural progenitor cell proliferation and neurogenesis in the striatum after focal ischemic injury in a mouse model. The present study shows that providing an appropriate environment for the neuronal differentiation of newborn neurons that migrate toward ischemic lesions improves functional recovery after ischemic stroke. We used lentivirus-mediated gene transfer of Wnt3a-HA into the ischemic striatum of a mouse model to enhance neurogenesis. Studies have shown that Wnt3 is expressed in the subgranular zone neurogenic niche by astrocytes and regulates the differentiation of progenitor cells towards neurons. Moreover, Wnt signaling is critically involved in neurogenesis. Inhibition of Wnt signaling in the dentate gyrus reduces the level of newborn neurons and impairs spatial and object recognition in rats. Our study expands these findings, demonstrating that Wnt signaling is able to increase the survival of newly produced neurons also in the non-neurogenic niche. An important question revolves around the functional significance of strokeinduced neurogenesis.