Sleep Deprivation Disrupts cAMP Signaling in the Brain's Hippocampus

The effects of sleep deprivation, which include forgetfulness, impaired mental performance, and a decline in the ability to learn, are modulated at the molecular level by changes in the metabolism of 3', 5'-cyclic AMP (cAMP) in the hippocampus region of the brain.

Investigators at the University of Pennsylvania (Philadelphia, USA) worked with a mouse population that could be manipulated to mimic patterns of human sleep deprivation. In the current study, mice were kept awake for five hours, which was the equivalent of a brief period of sleep deprivation in a human.

They reported in the October 22, 2009, issue of the journal Nature that brief sleep deprivation altered hippocampal function. At the molecular level this was evidenced by the selective impairment of cAMP- and protein kinase A (PKA)-dependent forms of synaptic plasticity in the mouse hippocampus, reduced cAMP signaling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors maintained cAMP levels and reversed the sleep-deprivation-induced deficits in cAMP signaling, synaptic plasticity, and hippocampus-dependent memory.

Since these findings showed that brief sleep deprivation disrupted hippocampal function by interfering with cAMP signaling through increased PDE4 activity, the authors speculated that, "Drugs that enhance cAMP signaling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation."


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