Rather, the effects of X-irradiation are predominantly on neurogenesis. Sham-irradiated animals exposed to EEE had an abundance of DCX+ and EYFP+ cells (Figures 6F and 6J). Most of the EYFP+ cells expressed both DCX and NeuN (Figures 6N and 6R), indicating that mostly neurons are produced in the NSC-derived lineage under EEE conditions. However, the irradiated animals IWR-1 supplier exposed to EEE did not exhibit marked differences in the number of EYFP+ cells from the irradiated cohort exposed to standard housing (Figures 6D and 6E). Fate mapping revealed that the EYFP+ lineage in irradiated animals exposed to EEE, or to standard housing, consisted primarily of NSCs, with some astrocytes

and EYFP+GFAP−DCX−NeuN− round cells also present (Figures 6L, 6M, 6P, and 6Q). Comparison of X- to sham-irradiated animals exposed to EEE revealed a fate shift from a mostly neuronal to a predominantly NSC

fate of the lineage (Figure 6B). These results demonstrate that X-irradiation blocks accumulation of neurons, but not NSCs. Since EEE did not profoundly check details affect expansion of the NSC population, we concluded that NSC and neuronal fate specification is dissociable. The results above demonstrated that both NSCs and neurons were increasingly represented within the NSC lineage, and that fate specification was dissociable. Moreover, the data suggest that fate specification within the adult-born hippocampal NSC lineage is governed by regional differences. We hypothesized that the NSC lineage potential, NSC-neuron relationship, and ultimately NSC number may be subject to regulation by more naturally occurring experiences. Social isolation was previously demonstrated to decrease cellular proliferation and either neurogenesis in the hippocampus (Ibi et al., 2008 and Lu et al., 2003) and alter the effects of neurogenesis-promoting experiences (Stranahan et al.,

2006). Moreover, increased numbers of GFAP+ cells were reported after adrenalectomy (Gould et al., 1992). We asked whether social isolation and EEE induce changes in adult hippocampal neurogenesis by instructing a fate shift within the lineage toward NSC accumulation or neurogenesis. Animals were exposed to either social isolation or EEE, followed by stereology and fate-mapping analysis 1 and 3 months after TMX. After 1 month, EYFP+ cells appeared to accumulate in both socially isolated and EEE-exposed animals compared to animals housed under standard laboratory conditions (Figures 7D–7F). We noted that while there were fewer DCX+ cells in socially isolated (Figure 7A) compared to standard housed (Figure 7B) animals, more EYFP+ cells exhibited NSC morphology in the isolated group (Figure 7D). EEE profoundly increased neurogenesis and expanded the EYFP+ lineage (Figures 7C and 7F). Socially isolated animals had a significant increase in the proportion of EYFP+ NSCs [t(6) = −3.181, p = 0.