Advertisement
According to a recent study published Dec. 3 in the journal Science Advances, tiny sacs called vesicles that carry instructions being passed between brain cells may be constantly leaking energy, and that leakage is likely a trade-off for the brain being ready to fire at all times.
“The brain is considered a very expensive organ to run,” said senior author Timothy Ryan, a professor of biochemistry at Weill Cornell Medicine in New York City.
Scientists previously assumed that the brain’s energy drain was due to the fact that it is electrically active, which means that brain cells, or neurons, are constantly firing electrical signals to communicate, a process that uses a lot of adenosine 5′-triphosphate, an energy molecule (ATP).
Clinical investigations have shown that the brains of persons in a vegetative state or coma, which means they have very little electrical brain activity, still require tremendous amounts of energy, Ryan told Live Science. So neuroscientists were left with a puzzle: if electrical activity isn’t consuming all of the brain’s energy, what is?
Advertisement
Ryan and his team have been studying synapses, which are brain connections where neurons meet and communicate by releasing tiny vesicles containing chemical messengers called neurotransmitters.
They previously demonstrated that activated synapses consume a significant amount of energy. However, researchers discovered that synapses spend a lot of energy even when neurons aren’t firing in a new study in which they used a poison to inactivate rat neuron synapses in lab dishes and then analysed ATP levels inside the synapses.
To figure out why, researchers disabled several pumps on the surfaces of the tiny vesicles that transport neurotransmitters and other molecules in and out, depriving synapses of fuel. They used a fluorescent microscope to scan the synapses and calculate how much ATP the synapse had burned.
They discovered that a “proton pump” was responsible for nearly half of the energy consumed in the resting synapse. The researchers discovered that because the vesicles were always “leaking” protons, the proton pump had to keep operating and using ATP.
Inactive synapses pre-load these vesicles with neurotransmitters so they can be launched at any time.
They do this with the help of a second pump that resides on the vesicle surfaces. Transporter proteins are a type of pump that change shape to carry neurotransmitters inside the vesicle and then grab a proton from inside the vesicle, change shape again, and spit the proton out. The vesicles must have a larger concentration of protons within than in their surrounds for this process to work.
However, the researchers discovered that the transporter proteins continued to alter form even after the vesicles were full of neurotransmitters. They continued to spew protons out even though they weren’t delivering neurotransmitters into the vesicles, necessitating the proton pump to keep operating to replenish the vesicle’s protons reserve.
The research was done on rat neurons in the lab, but because “the machinery involved is extraordinarily highly preserved” between rats and people, Ryan believes the findings would apply to human brains as well.
It’s unclear why our brains have this leakage, but he believes the easy shape shift is a trade-off for vesicles being able to store neurotransmitters quickly.
“If we had a way to safely lower this energy drain and thus slow brain metabolism, it could be very impactful clinically,” Ryan adds.