Hippocampal neurogenesis is reduced by sleep fragmentation in the adult rat

Abstract

The adult hippocampal dentate gyrus (DG) is a site of continuing neurogenesis. This process is influenced by a variety of physiological and experiential stimuli including total sleep deprivation (TSD). In humans, sleep fragmentation (SF) is a more common sleep condition than TSD. SF is associated with several prevalent diseases. We assessed a hypothesis that SF would suppress adult neurogenesis in the DG of the adult rat. An intermittent treadmill system was used; the treadmill was on for 3 s and off for 30 s (SF). For sleep fragmentation control (SFC), the treadmill was on for 15 min and off for 150 min. SF was conducted for three durations: 1, 4 and 7 days. To label proliferating cells, the thymidine analog, 5-bromo-2-deoxyuridine (BrdU), was injected 2 h prior to the end of each experiment. Expression of the intrinsic proliferative marker, Ki67, was also studied. SF rats exhibited an increased number of non-rapid eye movement (NREM) sleep bouts with no change in the percent of time spent in this stage. The numbers of both BrdU-positive cells and Ki67-positive cells were reduced by approximately 70% (P<0.05) in the SF groups after 4 and 7 days of experimental conditions whereas no differences were observed after 1 day. In a second experiment, we found that the percentage of new cells expressing a neuronal phenotype 3 weeks after BrdU administration was lower in the SF in comparison with the SFC group for all three durations of SF. We also examined the effects of SF on proliferation in adrenalectomized (ADX) animals, with basal corticosterone replacement. ADX SF animals exhibited a 55% reduction in the number of BrdU-positive cells when compared with ADX SFC. Thus, elevated glucocorticoids do not account for most of the reduction in cell proliferation induced by the SF procedure, although a small contribution of stress is not excluded. The results show that sustained SF induced marked reduction in hippocampal neurogenesis.

The ecological relevance of sleep: the trade-off between sleep, memory and energy conservation

“…Many factors resulting in reduced neurogenesis rates also result in deteriorated memory performance, and sleep deprivation in particular has also been linked to lowered cell proliferation rates and neuronal maturation rates in the hippocampus (Guzman-Marin et al 2003, 2008Hairston et al 2005). This result, however, does not appear to be mediated by stress, as adrenalectomized rats also show a reduction in neurogenesis rates following sleep deprivation (Mueller et al 2008; see also Guzman-Marin et al 2007;Meerlo et al 2008). A reduction in REM sleep in particular may be responsible for the reduction in neurogenesis rates (Guzman-Marin et al 2008;Mueller et al 2008), although more research is required to completely separate the effects of SWS and REM sleep.…”

Validation of a novel method to interrupt sleep in the mouse

“…However, these methods have little face validity to model the significant issue of interrupted sleep, which in humans rarely results in total sleep deprivation. Hence, techniques have recently been developed to interrupt sleep in rodents on a repetitive basis, specifically to examine the consequences of sleep disruption without total sleep loss (Bjorness et al, 2009;Guzman-Marin et al, 2007;McKenna et al, 2007;Polotsky et al, 2006;Ramesh et al, 2009;Tartar et al, 2006). These studies have been based on different techniques including a treadmill cage, with the treadmill in motion intermittently, or a mechanical device that operates intermittently within the cage or intermittent enforced hypoxia.…”

Brain Restoration: A Function of Sleep

“…, 1 9 8 9 ) . I n a d d i t i o n t o p h y s ical deterioration, cognitive processes are severely affected by sleep deprivation; TSD or prolonged sleep fragmentation produces a decrease in cellular proliferation (Guzmán-Marín et al, 2003) and neurogenesis (García-García et al, 2011;Guzmán-Marín et al, 2007;Guzmán-Marín et al, 2005) in the hippocampus of adult rats. Furthermore, differentiation and survival of new cells in this region are affected by SD (García-García et al, 2011;Roman et al, 2005).…”