Enriched Environment Attenuates Cell Genesis in Subventricular Zone After Focal Ischemia in Mice and Decreases Migration of Newborn Cells to the Striatum

Abstract

Background and Purpose-Cells proliferate continuously in the adult mammalian brain, and in rodents, cell genesis is affected by housing conditions and brain injury. Increase in neurogenesis after brain ischemia has been postulated to be linked to functional recovery after stroke. Housing rodents in an enriched environment improves motor function after stroke injury. We have investigated whether changes in cell genesis can explain the beneficial effects of an enriched environment. Methods-Intact mice and mice subjected to transient occlusion of the middle cerebral artery were exposed to an enriched environment for 1 month. Bromodeoxyuridine was injected daily to label proliferating cells during the first postischemic week. Newborn cells were analyzed immunohistochemically after 4 weeks. Results-The enriched environment increased neurogenesis in the dentate gyrus in both intact and stroke-injured animals. An increased number of newborn cells was found in the subventricular zone of stroke-injured mice, but not in injured mice exposed to an enriched environment. Also, the number of newborn astrocytes (BrdUϩ/S-100␤ϩ cells), neuroblasts (dcxϩ cells), and reactive astrocytes (vimentin mRNA) in the striatum ipsilateral to the ischemic injury was markedly attenuated and new adult neurons (BrdUϩ/NeuNϩ) were not found. The enriched environment did not affect infarct size or mortality. Conclusions-An enriched environment after experimental stroke increased neurogenesis in the hippocampus, whereas there was a decreased cell genesis and migration of neuroblasts and newborn astrocytes in the striatum.

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

“…Other genes regulated by EE may be involved in remodelling axonal connections (GPIanchored membrane protein 1, Tissue inhibitor 4, Vasodilator-stimulated phosphoprotein). Altogether, these results support the proposition that EE induces a profound structural changes and reorganization of striatal neurons (Bezard et al, 2003;Nygren et al, 2006;Spires et al, 2004). For example, it has been shown EE induces long-lasting adaptations such as increases in spine density and arborisation in the striatum of rats (Comery et al, 1996;Kolb et al, 2003a,b).…”

RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats

“…As previously reported, an increase in neurogenesis following ischemia has been considered to be necessary for functional recovery after stroke [19,20] . Beclin1-dependent autophagy has been associated with neurogenesis in several models [21,22] .…”

Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes

“…Enhanced neurogenesis has been suggested to occur in stroke patients (Jin et al, 2006, Macas et al, 2006. The notion that enhanced proliferation of NSPCs following stroke promotes functional recovery (Nygren et al, 2006, Thored et al, 2006) makes these findings potentially clinically relevant. The ambiguous response of microglia (pro-/anti-inflammatory) to injury depends on the types of stimulus (Hanisch and Kettenmann, 2007) and receptor activation (Ribes et al, 2009),…”