Physiological reviewNew neurons in the adult brain: The role of sleep and consequences of sleep loss
Section snippets
Neurogenesis in the adult brain
It has long been a central dogma in neuroscience that the mammalian brain can no longer generate new neurons once it reaches adulthood. However, contrary to this dogma, research over the last few decades has now firmly established that even the adult brain contains undifferentiated progenitor cells that give rise to new neurons.*1, *2, 3 While much of our current knowledge on neurogenesis in the adult mammalian brain is based on studies in laboratory rodents, the production of new neurons in
Daily rhythms in hippocampal cell proliferation
Sleep displays a clear circadian or daily rhythm that is governed by an endogenous biological clock located in the suprachiasmatic nucleus of the hypothalamus.31, 32 Therefore, if sleep plays a direct role in adult neurogenesis, one might expect to see a daily rhythm in cell proliferation and expression of neurogenic markers that parallels the sleep–wake rhythm. On the other hand, one has to bear in mind that a daily rhythm in cell proliferation would not necessarily be related to sleep per se
Effects of sleep deprivation and sleep disruption
To examine the role of sleep in neurogenesis, various studies have experimentally deprived or disrupted sleep in rodents for different durations, ranging from one to several days. While some of these studies applied prolonged total sleep deprivation for several days as a first approach to explore the relationship between sleep and neurogenesis, a number of experiments were specifically designed to better mimic sleep restriction or sleep disorders as they occur in humans, albeit in a severe
Sleep deprivation, the role of stress and other mechanisms
The finding of reductions in cell proliferation and neurogenesis after sleep deprivation or sleep disruption suggest that sleep itself promotes the production of new cells and neurons. However, the mechanisms by which sleep affects different aspects of neurogenesis are unknown. The fact that cell proliferation does not appear to be diminished by short sleep deprivation of less than a day,*34, 38, 39, *40 and the finding that reduced proliferation after prolonged sleep deprivation does not
Sleep deprivation, learning and neurogenesis
One important issue concerning the relationship between sleep and neurogenesis has only reached sparse attention. Most studies so far examined effects of sleep deprivation on basal rate of cell proliferation and neurogenesis. However, the importance of sleep may not just lie in regulating basal rates of neurogenesis but, rather, mediating changes in neurogenesis associated with, for example, learning.
Many studies suggest that sleep plays a role in learning and memory formation.67, 68, 69
Sleep disturbance and the human hippocampus
Although most of the current knowledge on adult neurogenesis is derived from studies in laboratory rodents, the generation of new neurons in the adult brain has been confirmed in humans as well.4 In elderly cancer patients that were injected with BrdU, postmortem analysis of brain tissue and immunostainings for BrdU together with specific neuronal markers unequivocally demonstrated the existence of proliferating cells and generation of new neurons in the DG of the hippocampus. Nonetheless,
Acknowledgments
This paper is the result of a joint symposium at the 5th World Sleep Congress in Cairns, Australia, September 2007. The writing of the manuscript was supported by the Netherlands Organization for Scientific Research (NWO grant 864.04.002 to PM).
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