Sleep deprivation leads to elevated PDE4
Kofi
are associated with autism and dopamine production. They also regulate
tight junction gaps.
http://www.sciencedaily.com/releases/2009/12/091215160900.htm
Enzyme Behind Effects of Sleep Deprivation Discovered
ScienceDaily (Dec. 16, 2009) � There is hope for those who miss one
night too many or whose children keep them up at night. The unwelcome
effects of a bad night's sleep -- forgetfulness, impaired mental
performance -- can be dealt with by reducing the concentration of an
enzyme in the brain.
These are the conclusions of research published by Rubicon-grant winner
Robbert Havekes and colleagues in the 22 October issue of Nature.
Millions of people are regularly plagued by sleep deprivation. This can
lead to both short-term and long-term problems with memory and learning
capacity. How sleep deprivation causes these kinds of problems was
largely unknown up to now. Havekes and his colleagues discovered that
sleep deprivation in mice undermines the function of a specific
molecular mechanism in the hippocampus, the area of the brain
responsible for consolidating new memories.
Enzyme inhibition
The researchers kept mice awake for five hours. They found increased
levels and activity of the enzyme PDE4 and lower levels of the molecule
cAMP in these mice. cAMP plays a crucial role in the formation of new
connections between brain cells in the hippocampus and the strengthening
of old ones. And without these processes we cannot learn.
The researchers inhibited the activity of the PDE4 enzyme and discovered
that this counteracts the effects of sleep deprivation. Lack of sleep
leads to an increased PDE4 activity which then blocks the action of
cAMP. Consequently fewer connections being formed or strengthened in the
hippocampus. This is the first report of researchers 'saving' synaptic
plasticity (the ability to develop and strengthen new connections) from
the effects of sleep deprivation.
The discovery not only shows how a lack of sleep leads to problems, but
also how these problems can be solved. Drugs that stimulate the action
of cAMP may make it possible to counteract the effects of sleep
deprivation. Neurobiologist Robbert Havekes received a grant from NWO's
Rubicon programme in 2007. Rubicon offers researchers who have recently
obtained their doctorate the opportunity to gain experience at a top
institute abroad. Havekes is currently working with Ted Abel's group at
the University of Pennsylvania.
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Story Source:
Adapted from materials provided by NWO (Netherlands Organization for
Scientific Research).
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Journal Reference:
1. Vecsey et al. Sleep deprivation impairs cAMP signalling in the
hippocampus. Nature, 2009; 461 (7267): 1122 DOI: 10.1038/nature08488