A week of urolithin A injections improved memory and reduced brain inflammation after sleep loss in mice. Digest
The effects of lost sleep on memory may depend partly on how well brain cells control inflammation and maintain their energy supply. Researchers tested whether urolithin A, a compound made by gut microbes from food components, could protect memory in mice when given before sleep deprivation.
Researchers randomly assigned 3-month-old and 12-month-old mice to saline control injections or urolithin A injections at 2.5 or 10 mg per kilogram of body weight for seven days before 24 hours of sleep deprivation. An intermittently moving treadmill kept the animals awake, while rested groups receiving the same treatments spent the same time in the apparatus with pauses long enough to allow sleep.
- Among sleep-deprived mice, both doses improved memory in both age groups compared with saline.
- Urolithin A reduced activation of the brain's supporting and immune cells and several inflammatory signals in the hippocampus.
- Treatment also countered changes in proteins that help maintain mitochondria, the cell's energy-producing structures.
- The higher dose protected against the loss of neuron branches in aged mice. The lower dose did not show a clear effect on this measure.
Sleep loss can activate the brain's immune cells, releasing inflammatory signals that interfere with mitochondria. Impaired mitochondria can generate more reactive molecules that damage cells and further fuel inflammation. Cells help limit this damage through mitophagy, a cleanup process that removes and recycles defective mitochondria. Urolithin A may help interrupt this cycle by reducing inflammatory signaling while supporting mitochondrial cleanup. Together, these actions could help neurons maintain the energy supply and connections needed for memory.
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The experiment suggests that at least part of the memory response to acute sleep loss is biologically modifiable. However, a week of injections before a defined period of sleep deprivation provides evidence about prevention in mice, not about using an oral supplement to undo a poor night's sleep.
In this clip, I discuss urolithin A and the evidence linking it to mitophagy.