This week’s Nature featured a Letter ¹ by Vecsey and colleagues entitled, Sleep deprivation impairs cAMP signalling in the hippocampus.

As an aside, a good title for the Good Paper Journal Club, were it not moribund from lack of time for people to keep it alive. And I see why this subject appealed to the editors, since it can appeal to all of us. Who among my readers is not sleep-deprived at some point or another?

I am another researcher experimenting on herself (how the sleep deprivation is acquired is another story, we’ll put it in Supplemental Methods, shall we?). How much short-term memory non-consolidation will I be able to tolerate until I actually forget to get up and pour more coffee? (Or: will I forget where I placed the mug?)

Caffeine is a non-specific phosphodiesterase (PDE) inhibitor. By inhibiting PDEs, caffeine prevents the PDE enzymes from being so quick about converting cyclic adenosine monophosphate back into its non-cyclic form.

In the other direction, epinephrine (of the famous epi pen) will activate other enzymes that push in the other direction, converting other derivatives back into cAMP.

In adrenalin rushes and caffeine highs, you are alert, and can have side effects such as heart palpitations. Having more cAMP around is a good way to rapidly relax bronchial (and uterine?) smooth muscle – hence, good for rapid relief for asthmatics, and curiously, as a vasoconstrictor, relieving Quincke’s edema or migraine, respectively.

Well, the article in question showed why brief sleep deprivation in a mouse model leads to difficulty in some memory tasks stored in the hippocampus. The lack of cAMP means the synapses, the major communication connections between neurons, don’t change in response to use, they way they should. In particular, it’s because there is too much of one of the PDEs around – it seems to be synthesized in response to the sleep deprivation – specifically, the PDE4A5 isoform of the PDE4 enzyme.

Treatment of mice with [broad, but also more specific] phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory.

While the most specific PDE4A5 inhibitors are being developed to rescue synaptic plasticity and memory deficits produced by a brief period of sleep deprivation and enable the consolidation and persistence of memory, would you please brew me another strong, black cup of java?

Maybe that third cup will help me remember to save all my changes in both open spreadsheets when I close the program, and also to remember that the dialogue “Save changes?” is not the same as “Close the program?” when my itchy trigger finger on the mouse hovers over the “No” response.

If only I had a counter to see how many times I had to change windows, and go back and double-check, when flipping between the article, PubMed, and this post. I had better go try to terminate my test of the relevance of the sleep-deprivation mouse model to memory behavior of a scientific peer, this weekend.
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¹ Nature 461, 1122-1125 (22 October 2009) doi:10.1038/nature08488