Here we show that depression-prone GR
+/−
mice exhibit a significant net reduction of adult hippocampal neurogenesis. GR
+/−
mice represent a particularly valuable animal model of depression because they reflect HPA system dysregulation which is a hallmark of a subgroup of depressive disorders in humans [
3]. Our observation is in line with the concept that neurogenesis has a role in the etiopathogenesis of mood disorders and contributes to the therapeutic actions of antidepressants [
6,
16,
22]; but see also [
10,
19,
24].
A number of current studies have provided novel insights into the link between depression-related behaviors and altered neurogenesis. In particular, recent work has shown that ‘learned safety’, as opposed to learned helplessness is associated with increased survival of new neurons and increased BDNF levels in hippocampus and that conversely, ablation of neurogenesis retards safety learning [
18]. Several other recent studies also demonstrate a link between BDNF signaling, neurogenesis, and behavior [
1,
15,
21]. In particular, ablation of BDNF receptor trkB in neural precursor cells results in impaired neurogenesis. When exposed to chronic antidepressant treatment or wheel-running, no increase in neurogenesis has been observed in these mice [
15]. Furthermore, ablation of trkB also renders the animals behaviorally insensitive to antidepressive treatment in depression- and anxiety-like paradigms [
15]. Lack of trkB in adult progenitors also results in disturbed organization of basic synaptic connections of newly generated neurons and impaired neurogenesis-dependent long-term potentiation, accompanied by compromised survival of newly generated cells and increased anxiety-like behaviors [
1]. Reduced net hippocampal neurogenesis in GR
+/−
mice as reported here fits well with these reports. Importantly, we have previously demonstrated a significant reduction of BDNF protein concentrations in hippocampus of GR
+/−
mice [
20]. However, it should be noted that the reduction in neurogenesis in GR
+/−
mice which emerged in this comparatively large experiment was only moderate. This may support the notion that in addition to reduced neurogenesis, other mechanisms may also contribute prominently to the depression-related behavioral phenotype of GR
+/−
mice [
6].