Friday, December 28, 2007

New mechanism explains glucose effect on wakefulness

New mechanism explains glucose effect on wakefulness

New mechanism explains glucose effect on wakefulness
One of the body's basic survival mechanisms is the neural machinery that triggers the hungry brain to the alertness needed for seeking food. That same machinery swings the other way after a hearty meal, as exemplified by the long and honored custom of the siesta. However, scientists have understood little about how the basic energy molecule, glucose, regulates such wakefulness and other energy-related behaviors.

Now, in an article in the June 1, 2006, Neuron, Denis Burdakov of the University of Manchester and his colleagues have pinpointed how glucose inhibits neurons that are key to regulating wakefulness. In the process, they have discovered a role for a class of potassium ion channels whose role has remained largely unknown. Such ion channels are porelike proteins in the cell membrane that affect cellular responses by controlling the flow of potassium into the cell.

The researchers set out to discover how glucose inhibits a particular class of glucose-sensing neurons that produce tiny proteins called orexins, which are central regulators of states of consciousness.

Burdakov and colleagues wrote, "These cells are critical for responding to the ever-changing body-energy state with finely orchestrated changes in arousal, food seeking, hormone release and metabolic rate to ensure that the brain always has adequate glucose."

Malfunction of orexin neurons can lead to narcolepsy and obesity, and researchers have also found evidence that orexin neurons play a role in learning, reward-seeking, and addiction, the researchers wrote.

"Considering these crucial roles of orexin neurons, their recently described inhibition by glucose is likely to have considerable implications for the regulation of states of consciousness and energy balance," wrote Burdakov and his colleagues. "However, as in other glucose-inhibited neurons, it is unknown how glucose suppresses the electrical activity of orexin cells." What's more, they wrote, "Because the sensitivity of orexin cell firing to the small changes in extracellular glucose that occur between normal meals has never been tested, the daily physiological relevance of their glucose sensing is also unknown."

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