Social isolation delays the positive effects of running on adult neurogenesis

Abstract

Social isolation can exacerbate the negative consequences of stress and increase the risk of developing psychopathology. However, the influence of living alone on experiences generally considered to be beneficial to the brain, such as physical exercise, remains unknown. We report here that individual housing precludes the positive influence of short-term running on adult neurogenesis in the hippocampus of rats and, in the presence of additional stress, suppresses the generation of new neurons. Individual housing also influenced corticosterone levels--runners in both housing conditions had elevated corticosterone during the active phase, but individually housed runners had higher levels of this hormone in response to stress. Moreover, lowering corticosterone levels converted the influence of short-term running on neurogenesis in individually housed rats from negative to positive. These results suggest that, in the absence of social interaction, a normally beneficial experience can exert a potentially deleterious influence on the brain.

Intrahippocampal Transplantation of Transgenic Neural Precursor Cells Overexpressing Interleukin-1 Receptor Antagonist Blocks Chronic Isolation-Induced Impairment in Memory and Neurogenesis

“…Previous studies on the effects of chronic stress on hippocampal neurogenesis demonstrated decreased cell proliferation in the dentate gyrus following chronic isolation (Dong et al, 2004), as well as several other chronic stressors (Simon et al, 2005; Lee et al, 2006;. Chronic social isolation also exacerbated the effect of another chronic stressor (daily foot-shock for 3 weeks) on the production of new hippocampal neurons (Westenbroek et al, 2004), and precluded the positive influence of short-term running on neurogenesis (Stranahan et al, 2006). Our findings are consistent with these reports, demonstrating that chronic isolation decreased the production of new neurons, which has been implicated in some hippocampal-dependent learning and memory tasks (Shors et al, 2001;Shors, 2004;Saxe et al, 2006).…”

“…Furthermore, exposure to acute psychological stressors, such as short-term (3-5 h) isolation, increased hippocampal IL-1 levels and produced memory impairments that were completely blocked by an intrahippocampal injection of IL-1ra (Barrientos et al, 2003(Barrientos et al, , 2004. Stressful conditions, such as social isolation, also influence several aspects of neural plasticity, including hippocampal neurogenesis (Dong et al, 2004;Westenbroek et al, 2004;Stranahan et al, 2006), which is critically important for some hippocampal-dependent learning and memory tasks (Shors et al, 2001(Shors et al, , 2002Saxe et al, 2006;Winocur et al, 2006). We have recently demonstrated that chronic mild stress, as well as chronic administration of IL-1b, markedly reduces hippocampal neurogenesis .…”

Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons

“…Immunolabeling for BrdU and Ki67 was carried out as described 15 . Full description of the methods for brightfield and fluorescence tissue labeling are available in Supplementary Methods.…”

“…Full description of the methods for brightfield and fluorescence tissue labeling are available in Supplementary Methods. We quantified single-and double-labeled cells using standard protocols 15 . Detailed cell counting criteria are available in Supplementary Methods.…”

“…Long-term potentiation (LTP) of synaptic transmission, believed to be a cellular mechanism of learning and memory, is impaired in the dentate gyrus of rats with streptozocin-induced diabetes 10 . Diabetic animals also exhibit lower rates of adult neurogenesis 11 , while exercise and dietary energy restriction, which have anti-diabetic effects, can enhance synaptic plasticity 12,13 and neurogenesis 12,14,15 . Because cognitive ability is impaired in subjects with either type 1 or type 2 diabetes, and in animal models of both types of diabetes, it is unlikely that global changes in insulin levels are directly responsible for impaired neuronal plasticity.…”