May 6, 2011

Sleep Pathway Discovered

(Ivanhoe Newswire) -- Worms may help researchers understand more about sleep. A team of neurobiologists at Brown University and elsewhere discovered that "Notch," a signaling pathway found in all animals, is directly involved in sleep in the nematode C. elegans.

"We understand sleep as little as we understand consciousness," Anne Hart, associate professor of neuroscience at Brown and the paper's senior author, was quoted as saying. "We're not clear why sleep is required, how animals enter into a sleep state, how sleep is maintained, or how animals wake up. We're still trying to figure out what is critical at the cellular level and the molecular level."

The researchers found adult nematodes without Notch pathway genes have their Notch receptors turned off and do not avoid octanol (an odious-smelling substance) like normal worms do. Dr. Hart was surprised to find that adult nematodes with an overexpression of the osm-11 gene (a Notch pathway gene) started taking spontaneous naps. Normally, adult nematodes spend all of their time moving. "It was the oddest thing I'd seen in my career," Hart said.

Other experiments showed that the worms lacking osm-11 and the related osm-7 genes were hyperactive and exhibited twice as many body bends each minute compared to normal nematodes. The more Notch signaling was turned on, the sleepier the worms became. When it was suppressed, the worms would go into overdrive and become too active.

In humans, the gene called Deltalike1 is most similar to osm-11. It is expressed in regions of the brain associated with the sleep-wake cycle.

Researchers say manipulating Notch signaling is tricky because it is implicated in a lot of different activities in the body. "Too much Notch signaling can cause cancer, so we would have to be very targeted in how we manipulate it," Hart said. "One of the next steps we're going to take is to look at the specific steps in Notch signaling that are pertinent to arousal and quiescence."

SOURCE: Current Biology, May, 2011