Neurological

Scientists explain why neurons use up so much energy even when they are at rest

Pound for pound, the brain uses far more energy than other organs, and mysteriously it remains a fuel guzzler even when its neurons don’t send signals called neurotransmitters to each other. Now researchers at Weill Cornell Medicine have found that the process of packaging neurotransmitters could be responsible for this energy loss.

In their study, reported December 3 in Science Advances, they identified tiny capsules called synaptic vesicles as a major source of energy expenditure in dormant neurons. Neurons use these vesicles as containers for their neurotransmitter molecules, which they fire from communication ports called synaptic terminals to signal other neurons. The packing of neurotransmitters into vesicles is a process that uses chemical energy, and the researchers found that this process is inherently energy-leaky — so leaky that it continues to use significant energy even as the vesicles fill and the synaptic terminals are inactive.

These results help us better understand why the human brain is so vulnerable to its fuel supply being disrupted or weakened.

Lead Author Dr. Timothy Ryan, professor of biochemistry and biochemistry in anesthesiology at Weill Cornell Medicine.

Dr. Ryan and his lab have shown in recent years that neurons’ synaptic terminals, bud-like growths from which they fire neurotransmitters, are large consumers of energy when they are active and are very sensitive to any disruption in their fuel supply. In the new study, they examined fuel consumption in synaptic terminals during inactivity and found that it is still high.

They discovered that this high resting-state fuel consumption is largely due to the vesicle pool at synaptic terminals.

Researchers discovered that what essentially happens is a loss of energy from the vesicle membrane, “proton leakage,” so a special “proton pump” enzyme in the vesicle has to keep working, consuming fuel in the process, even when the vesicle is already full of neurotransmitters -Molecules.

The experiments pointed to proteins called transporters as likely sources of this proton leakage.

Although the leakage per vesicle would be tiny, there are at least hundreds of trillions of synaptic vesicles in the human brain, so the energy loss would really add up, Dr. Ryan.

The discovery is a significant advance in understanding the basic biology of the brain. In addition, the brain’s susceptibility to disruption of its fuel supply is a major problem in neurology, and metabolic deficiencies have been identified in a variety of common brain diseases, including Alzheimer’s and Parkinson’s. This line of inquiry could ultimately help solve important medical mysteries and suggest new treatments.

If we had a way to safely lower this energy loss and thereby slow down brain metabolism, it could be very powerful clinically.

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