New Mechanism Explains Glucose Effect On Wakefulness

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New Mechanism Explains Glucose Effect On Wakefulness

http://www.medicalnewstoday.com/medicalnews.php?newsid=44376

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.

Wrote Burdakov and colleagues, " 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, wrote the researchers.

" 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. "

In their experiments, the researchers engineered mice to produce a

fluorescent protein only in orexin neurons. Thus, the researchers

could isolate the neurons in brain slices from the mice and perform

precise biochemical and electrophysiological studies to explore how

glucose acted on those neurons. In particular, the researchers

performed experiments in which they exposed the neurons to the subtle

changes in glucose levels known to occur in daily cycles of hunger

and eating.

Their experiments showed that glucose inhibits orexin neurons by

acting on a class of potassium ion channels known as " tandem pore "

channels, about which little was known.

" Together, these results identify an unexpected physiological role

for the recently characterized [tandem pore potassium] channels and

shed light on the long-elusive mechanism of glucose inhibition, thus

providing new insights into cellular pathways regulating vigilance

states and energy balance, " wrote Burdakov and colleagues.

" These results provide evidence that the firing rate of orexin cells

is sensitive to changes in glucose that correspond to fluctuations

occurring normally during the day and also show that the same

electrical mechanism is involved in sensing both subtle and extreme

changes in glucose, " they wrote.

What's more, they wrote, their finding that subtle changes in glucose

levels affect firing of orexin " raises the possibility that, besides

being important for adaptive responses to starvation, modulation of

orexin cells by glucose has a much wider behavioral role,

contributing to the continuous daily readjustments in the level of

arousal and alertness. "

The researchers concluded that their findings " provide important new

insights into how the brain tunes arousal and metabolism according to

body-energy levels. "

[Guest guest]

Hello Gretchen,

Quod Erat Demonstrandum

EdM from NH (lol)