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Vecsey CG, Baillie GS, Jaganath D, Havekes R, Daniels A, Wimmer M, Huang T, Brown KM, Li XY, Descalzi G, Kim SS, Chen T, Shang YZ, Zhuo M, Houslay MD, Abel T. Sleep deprivation impairs cAMP signalling in the hippocampus. Nature . 2009 Oct 22 ; 461(7267):1122-5. PubMed Abstract

Comments on Paper and Primary News
Primary News: cAMP Signaling Links Sleep Disturbances and Cognitive Deficits

Comment by:  David J. Porteous, SRF Advisor
Submitted 29 October 2009 Posted 30 October 2009
  I recommend this paper

This is a really interesting study, which should stimulate new thinking and experimentation. cAMP-dependent signaling is a core component of the mammalian circadian pacemaker (O'Neill et al., 2008). Do those schizophrenic (and indeed non-schizophrenic) patients with sleep disorder show direct evidence for altered PDE4 signaling? If so, does genetic variation in the DISC1-PDE4 complex contribute to this and indicate a differential molecular diagnosis? Clapcote et al. (2007) reported differential effects of Disc1 missense mutations Q31L and L100P on brain PDE4 activity and on behavioral response to rolipram. Do these strains and indeed other Disc1 mutant mice have disturbed sleep patterns?


O'Neill JS, Maywood ES, Chesham JE, Takahashi JS, Hastings MH. cAMP-dependent signaling as a core component of the mammalian circadian pacemaker. Science . 2008 May 16 ; 320(5878):949-53. Abstract

Clapcote SJ, Lipina TV, Millar JK, Mackie S, Christie S, Ogawa F, Lerch JP, Trimble K, Uchiyama M, Sakuraba Y, Kaneda H, Shiroishi T, Houslay MD, Henkelman RM, Sled JG, Gondo Y, Porteous DJ, Roder JC. Behavioral phenotypes of Disc1 missense mutations in mice. Neuron . 2007 May 3 ; 54(3):387-402. Abstract

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Primary News: cAMP Signaling Links Sleep Disturbances and Cognitive Deficits

Comment by:  Robert Stickgold (Disclosure)Dara Manoach
Submitted 2 November 2009 Posted 3 November 2009
  I recommend this paper

Although disturbed sleep is a prominent feature of schizophrenia that has been recognized since Kraepelin (1919), its relation to the pathophysiology, signs, and symptoms of schizophrenia remains poorly understood. In healthy individuals, there is now overwhelming evidence that critical aspects of learning and memory consolidation depend on sleep. Yet, in spite of the ubiquity of sleep disorders in schizophrenia, they have generally been overlooked as a potential contributor to cognitive deficits. As recently reviewed by Manoach and Stickgold (2009), an emerging literature suggests that abnormal sleep in schizophrenia may contribute to these cognitive deficits through its impairment of sleep-dependent memory consolidation.

The finding by Vecsey et al. that sleep deprivation leads to an increase in transcription and translation of the gene coding for phosphodiesterase-4 (PDE4), and that inhibiting the action of PDE4 with the drug rolipram restores both normal cAMP levels and sleep-dependent memory consolidation in rodents,...  Read more

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