Tuesday, January 04, 2022

Brain drain: Why do neurons guzzle fuel even at rest?

Recommendable! Why the brain even at rest consumes large amounts of energy.

"... they identified tiny capsules called synaptic vesicles as a major source of energy consumption in inactive neurons. Neurons use these vesicles as containers for their neurotransmitter molecules, which they fire from communications ports called synaptic terminals to signal to other neurons.
Packing neurotransmitters into vesicles is a process that consumes chemical energy, and the researchers found that this process, energy-wise, is inherently leaky – so leaky that it continues to consume significant energy even when the vesicles are filled and synaptic terminals are inactive. ...
The observation that the brain consumes a high amount of energy, even when relatively at rest, dates back several decades to studies of the brain’s fuel use in comatose and vegetative states. Those studies found that even in these profoundly inactive states, the brain’s consumption of glucose typically drops from normal by only about half – which still leaves the brain as a high energy consumer relative to other organs. The sources of that resting energy drain have never been fully understood. ..."

From the abstract:
"The human brain is a uniquely vulnerable organ as interruption in fuel supply leads to acute cognitive impairment on rapid time scales. The reasons for this vulnerability are not well understood, but nerve terminals are likely loci of this vulnerability as they do not store sufficient ATP molecules and must synthesize them on-demand during activity or suffer acute degradation in performance. The requirements for on-demand ATP synthesis however depends in part on the magnitude of resting metabolic rates. We show here that, at rest, synaptic vesicle (SV) pools are a major source of presynaptic basal energy consumption. This basal metabolism arises from SV-resident V-ATPases compensating for a hidden resting H+ efflux from the SV lumen. We show that this steady-state H+ efflux is 1) mediated by vesicular neurotransmitter transporters, 2) independent of the SV cycle, 3) accounts for ~half of the resting synaptic energy consumption and 4) contributes to nerve terminal intolerance of fuel deprivation.
Nerve terminals consume large amounts of ATP even at rest
A large fraction of the resting metabolic burden arises from the V-ATPase
Steady-state V-ATPase activity is driven by a synaptic vesicle H+ leak
This H+ leak is mediated vesicular neurotransmitter transporters"

Brain drain: Why do neurons guzzle fuel even at rest? | Cornell Chronicle

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