Sleep Flushes Toxins from the Brain

Direct link to the research: http://www.gwern.net/docs/algernon/1995-rechtschaffen.pdf

The paper is titled "Sleep deprivation in the rat by the disk-over-water method." As the name implies, rats are suspended on a disk over water. They can't fall asleep without starting to drown. Thus they are kept awake.

The paper begins with, "Because short-term sleep deprivation (SD) may stimulate only sleep-promoting mechanisms, chronic SD may be required to elicit function-revealing deficits. However, the enforcement of chronic SD requires repeated, intrusive stimulation which can blur the interpretation of effects. Do they result from sleep loss or from the strong stimulation used to enforce SD? To simplify communication, we speak of the 'effects' of SD, but strictly speaking, SD studies are correlational. We apply stimuli to enforce SD and report the relationship between the ensuing sleep loss and changes in performance or physiology. However, the changes and the sleep loss could be independent responses to the stimulation. The interpretation that the changes result from sleep loss hinges on minimizing the contribu- tion of the deprivation-enforcing stimulation, which can be especially difficult when strong stimulation is used to en- force chronic SD."

There are two possibilities. Either rats being repeatedly almost-drowned doesn't contribute to death after 45 days, or it does. The paper goes on to demonstrate the steps they took to minimize the chance that almost-drowning rats resulted in death:

"Hypothermia had been suspected as a proximal cause of death [3,31,34] because all SD rats showed an eventual decline in intraperitoneal temperature (Tip); a decline to more than 1 °C below baseline in otherwise untreated SD rats has been a reliable indicator of impending death within a day or two. However, TSD rats kept warm by exogen- ous heating died nevertheless"

"A second possible cause of death is breakdown of body tissues due to catabolism, secondary to the high metabolic rate in TSD rats [3,14,31]. [...] Evidence against catabolism as a mediator of preterminal effects includes a lack of preterminal serum albumin de- cline in PSD rats [22] and the deaths of all rats in two TSD groups protected against catabolic effects, hypothy- roid rats and high-calorie diet rats. Thus tissue breakdown secondary to catabolism was not a necessary cause of death."

However, this third point is a key conflating factor:

"A third major candidate for proximal cause of death is organ failure secondary to systemic infection, as suggested by bacteremia, which Everson has observed in five of six TSD rats obviously near death [11]. We subsequently confirmed bacteremia in two additional preterminal TSD rats [20]. Very recently, we treated six TSD rats with antibiotic cocktails; five progressed to an apparently ter- minal condition nevertheless and were then killed (after 10-16 days of TSD). Neither heart blood samples, livers, kidneys, nor mesenteric lymph nodes showed aerobic bac- terial or fungal infection. The sixth rat died after 19 days; blood could not be drawn, but the other tissues were har- vested shortly thereafter and were also free of aerobic bacteria and fungi. These results indicate that microbial invasion is not a necessary cause of death in TSD rats."

If you read carefully, they begin by saying "almost-drowning rats eventually results in organ failure." They end with "microbial invasion is not a necessary cause of death."

I think it's possible that almost-drowning rats causes organ failure for reasons other than microbial infection. The fact that the rats progressed to a terminal condition even after antibiotics seems to support this hypothesis. Their organs failed anyway. I wonder if dunking them in water for a month had something to do with it, and not the sleep deprivation?

The paper seems to tiptoe around this point.

Note this quote: "Cells in the brain, probably the glial cells which keep nerve cells alive, shrink during sleep. This increases the size of the interstitial space, the gaps between brain tissue, allowing more fluid to be pumped in and wash the toxins away."

Neurons are powerful cells that are so active that they cannot even keep themselves healthy. The glial cells are there to help. If the glial cells are shrinking and (presumably) partially shutting down in order to efficiently clean out the brain, then sleep is an efficient engineering solution -- you are trading off having a super-active brain for ~16 hours at the cost of a less effective brain for ~8 hours.

There may be less efficient solutions that allow for 24 hours semi-wakefulness, we might be able to tune the total activity of the brain down for continuous operation, but being in a groggy half-asleep state all day is probably not what you were hoping for.