New drug target discovered for sleep deprivation

There's no mystery surrounding the cognitive consequences of a lack of sleep. Sleep deprivation commonly triggers learning and memory deficits--as just about anyone can attest to. But researchers at the University of Pennsylvania say they've discovered the molecular pathway that leads to cognitive impairment from sleep deprivation, and point to a possible cure.

Professor Ted Abel and his team found the pathway in the hippocampus, a region of the brain that plays a big role in memory and learning. The study showed that mice deprived of sleep had increased levels of the enzyme PDE4 and reduced levels of the molecule cAMP, which is crucial in forming new synaptic connections in the hippocampus, a key to learning. Researchers then treated the mice with PDE inhibitors, which rescued the sleep deprivation-induced deficits in cAMP signaling, counteracting some of the memory consequences of sleep deprivation.

"Our work has identified a treatment in mice that can reverse the cognitive impact of sleep deprivation," said Abel. "Further, our work identifies specific molecular changes in neurons caused by sleep deprivation, and future work on this target protein promises to reveal novel therapeutic approaches to treat the cognitive deficits that accompany sleep disturbances seen in sleep apnea, Alzheimer's disease and schizophrenia."

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