Unexpected Brain Cells Linked to Narcolepsy Sleep Attacks
A new study has identified a specific subset of brainstem neurons that may be responsible for sudden, involuntary sleep attacks in narcolepsy patients.
A new study has shed light on the mysterious sleep attacks that occur in narcolepsy patients. Researchers at the University of Toronto have discovered a specific subset of brainstem neurons that may be responsible for these episodes.
The study, published in PLOS Biology, found that GABA neurons in the sublaterodorsal tegmental nucleus (SLD) are a previously unrecognized trigger of sleep-attack episodes. These neurons aid in calming brain activity, but their role in the sleep-wake cycle is less clear.
The researchers worked with both healthy mice and mice bred to lack the chemical orexin, which is also missing in human narcolepsy type 1 (NT1). Using optogenetics, a technique that allows researchers to turn specific neurons off and on using light, they tested what happened when these SLD GABA neurons were turned off.
The findings suggest that in narcolepsy, when there is a lack of orexin, the brain is out of balance and these neurons become overly active at the wrong time. If they are silenced, sleep attacks can be prevented, and conversely, if they are activated, even when mice are eating or walking, they will fall asleep in less than a couple of seconds.
The SLD region is thought to control the rapid eye movement (REM) stage of sleep, but researchers were surprised to discover that activating SLD GABA neurons primarily promoted non-REM sleep. While GABA cells were thought to be important for controlling the timing of REM sleep, newer studies have suggested it's actually glutamate cells in the same region that are essential for REM sleep.
The study's lead author, Jimmy Fraigne, PhD, an assistant professor in the department of Cell and Systems Biology at the University of Toronto, is encouraged that if the right medication can specifically and exclusively silence SLD GABA neurons, it could prevent the uncontrollable sleepiness that patients experience.
| Neurons | Function | Effect |
|---|---|---|
| SLD GABA neurons | Calm brain activity | Promote non-REM sleep and trigger sleep attacks |
| Glutamate cells | Essential for REM sleep |
While a novel treatment based on the findings is still some time away, Fraigne is optimistic that understanding the mechanism behind narcolepsy sleep attacks may lead to a better approach to treatment, with fewer side effects.
“Until the discovery of orexin in the late 1990s and the establishment that it is the lack of orexin neurons that causes narcolepsy, we didn’t have a clear understanding of what could help patients,” explains Fraigne. “We show with our study that it is really a question of restoring the balance between wake and sleep tone that might lead to smoother outcomes with fewer side effects.”
