Feb. 9, 2016 

The need to sleep in humans and all other animals evolved as a way to prevent the toxic buildup of chemical messengers in brain cell membranes, a Dartmouth College scientist says.

The study appears in the journal Frontiers in Synaptic Neuroscience.

Many theories have been proposed to explain why we sleep, with the consensus being that it promotes brain health as well as physical health. Recent studies have found that when animals are sleeping or under anesthesia, the brain’s interstitial fluid, or the cerebrospinal liquid in spaces between tissue cells, acts as a neural janitor, removing waste that accumulates during wakefulness. But the evolutionary origin for the need to sleep in the animal kingdom -- essentially all organisms with nervous systems -- isn’t clear at the molecular level.

In a study last year in Biophysical Journal as well as earlier research, Robert Cantor, a professor of chemistry at Dartmouth, explored how general anesthesia works, which has been a mystery since it was first used in surgery in 1846. He used computational methods to explore the consequences of his hypothesis on synaptic neurotransmission, or how the signal from one neuron is chemically transmitted across the synapse to another neuron. It has long been known that neurotransmitter molecules are emitted at the presynaptic neuron, spread across the synapse and bind to specific (lock-and-key) sites on the receptor proteins embedded in the cell membrane on the postsynaptic neuron, and thereby activate these proteins. Cantor proposes that these neurotransmitters also absorb into the lipid bilayer in which these proteins are embedded, which strongly modulates the response of these receptors. The lipid bilayer is a membrane of two layers of fat molecules that make up cells’ protective outer barrier. Because this lipid bilayer mechanism doesn’t require binding to specific sites on the receptors, anesthetics modulate these proteins as well, inducing anesthesia, Cantor says.

In his latest study, Cantor suggests the evolutionary origin of the need to sleep involves lipid bilayers and synaptic transmission as discussed in his hypothesis above. Neurotransmitter molecules that enter the synapses are mostly cleared out, but not with 100 percent efficiency, so their concentration builds up in the brain’s interstitial fluid. If these neurotransmitter molecules were to reach a concentration at which they would absorb significantly to lipid bilayers, they would alter the behavior of membrane proteins such as postsynaptic receptors. To avoid the resulting damaging consequences, the neurotransmitter molecules must be cleared out of the interstitial fluid periodically, which occurs during sleep.

“It is estimated that even if only 0.1 percent of neurotransmitters escape reuptake, they would accumulate and absorb to bilayers in synapses of other receptors sufficiently to affect receptor activity, the harmful consequences of which are avoided by sleep,” Cantor says.

PDFs of the two studies are available on request.

Dartmouth Professor Robert Cantor is available to comment at Robert.S.Cantor@dartmouth.edu.

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