Authors of a recent Nature article about the effects of sleep deprivation (1), wrote “Millions of people regularly obtain insufficient sleep”. I suspect that the majority of these people are either students or new parents. Regardless of whether you fall into these two categories, I think everyone has struggled with the adverse effects of sleep deprivation, such as cognitive impairment and memory problems, at some point. Now, this Nature article provides us with a better understanding of the molecular mechanisms that cause these effects and, perhaps more importantly, hope that these effects can be reversed.
Vecsey et al. were studying the molecular mechanism by which sleep deprivation alters hippocampal function in mice. Since cyclic AMP (cAMP) and protein kinase A signaling is known to be involved in long-term potentiation (LTP), which is crucial for learning and memory, the authors decided to focus on this pathway. They found that brief periods of sleep deprivation increase activity and protein levels of phosphodiesterase 4 (PDE-4), an enzyme that degrades cAMP, and interfer with cAMP and protein kinase A signalling in hippocampal LTP. The authors then examined whether administering a PDE-4-selective inhibitor to sleep-deprived mice could rescue the impaired synaptic plasticity and hippocampus-dependent memory. Treatment with the PDE-4 inhibitor helped to eliminate this deficit, further supporting the hypothesis that disruption of cAMP signalling is responsible for the effects of sleep deprivation.
This is all well and good for sleep-deprived mice. What does this mean for humans, and will this study lead to new therapeutics that reduce or eliminate the effects of sleep deprivation? It is too early to tell, although it is tempting to think that such research might lead to a cure for late nights and early mornings. For the time being, however, we’ll have to settle for that extra cup of coffee.
- Vecsey, C.G. et al. (2009) Sleep deprivation impairs cAMP signalling in the hippocampus. Nature 461, 1122–5.
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