Our sleeping sickness

 

This post is about sleep biology. Sleep may be a cellular process. Lack of sleep may produce a substance that is a feedback loop for getting even sleepier.

The abstract: Hinard V, Mikhail C, Pradervand S, Curie T, Houtkooper RH, Auwerx J, Franken P, and Tafti M (2012). Key electrophysiological, molecular, and metabolic signatures of sleep and wakefulness revealed in primary cortical cultures. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (36), 12506-17 PMID: 22956841

Your loyal bloggist has been sick twice in 6 months, a record for us since we rarely get sick, and both times it has been the same illness: a fierce headache (and we don’t get headaches) and unbearable sleepiness, with a tinge of nausea. The first time we recovered in 7 days, and that was particularly inconvenient as we were a houseguest where we suppose we’ll never be invited again. This last time (the last 2 days) we’re better in roughly two and a half days (we’re not quite 100%).

The only time we think about sleep is when there is insufficient sleep. Occasionally we have chronic insomnia, but it’s cured easily with half a Tylenol-nighttime. Or watching C-Span.  (We refuse to take Ambien for fear what we’d do. See, “Ambien Cookbook.“*)  It’s only with this recent illness that we’ve been extraordinarily sleepy — we’d say it was truly Chronic Fatigue Syndrome but it’s not chronic.

So, we found Neuroskeptic’s note about some recent sleep research: “Brains in a dish need sleep too?” discussing a study of brain cells in a Petri dish. The cells, according to a variety of measures, seem to have a periodicity– a “sleep”  and “wake” cycle (our characterization).  Neuroskeptic and the comments go into all the ins and outs. But, the significance is that it could be that sleep is a cellular process, like cellular respiration or division or anything else that doesn’t need higher order brain direction.  While we’ve wondered about periodicity biology from time to time (the CLOCK gene, and stem-cell mobilization related to circadian oscillation here), the origin of such periodicity as a biological process — by clumps of cells in a plate — is pretty mind-blowing.

Another thing we thought was interesting is that (quoting from Neuroskeptic):

*  *  *

Finally – and this might end up being the most important bit – the authors compared the biochemistry of the ‘sleep deprived’ dishes to the ‘well rested’ ones. They found remarkably few major changes, but they did observe a significant increase in the levels of lysolipids.

Lysolipids are breakdown products of phospholipids, which make up the membranes of all living cells. When present in membranes, lysolipids can act as ‘detergents’, distorting their structure. That’s bad. These results suggest that sleep might serve to prevent the build up of lysolipids. If that pans out, it would mean that the function of sleep is very primitive, a fundamental biological necessity for any connected network of neurons, even what amounts to a random medley thrown together on a plate.

So, to overstate and oversimplify, when you’re sleep deprived, just say your cells overproduce lysolipids. (And this is not proved, we’re leaping to conclusions). Just say. And one effect of that is making your other cells weird out.

So we Googled and PUBMEDDED lysolipids. (The Let Me Google That For You link). We found maybe another possibly good thing. It relates to cannabis.

One receptor for some kinds of lysolipids** is GPR55 – an endocannabinoid receptor. (Here.)  GPR55 is a potential target for pain meds. So. . . does that mean that the lysolipid production binds the GPR55 so that you don’t feel anything when you’re sleeping?  Another paper (here) suggests that when lysophosphatidylinositol is bound to GPR55, neurites retract (and that would mean fewer neural networks, presumably). Consider: cocaine induces neural connections and keeps you wired, versus marijuana —  activating the cannabinoid GPR55 receptor — prunes dentrites. Is that why marijuana makes you sleepy and stupid?

So perhaps this lysolipid in the Petri dish of stressed out brain cells is really a good thing — it acts as the positive feedback loop for requiring sleep. When you don’t get enough sleep, there is more lysolipid binding to GPR55 making you numb and pruning your dendrites. The less sleep, the more lysolipid and the less pain and fewer dendrites you get. Plausible, no?

“But where is your self interest, Swivelchair?” you may ask. It’s this mysterious sleeping sickness. And so we  have diagnosed ourselves with some sort of lysogenic virus that degrades our cell membranes to this pesky lysolipid-making-us-stupidly-sleepy for two days straight. Normally, our SoCal curative is that we would take a jacuzzi to cook out the virus at the first sign of illness (a method we derived from some blood bankers***). But since we’ve moved, we don’t have a jacuzzi any more (bad planning on our part). No wonder we’ve been sick. Hmm.

 

 

* Sorry it’s paywalled. An Ambien Cookbook excerpt recipe : 

Icebox Mélange 
Ingredients: 
Entire contents of refrigerator 
1 Diet Snapple 
5 mg. Ambien 

Take Ambien, fall asleep.

Wait 2-3 hours, then sleepwalk to kitchen.

Devour everything in refrigerator (including all fancy mustards and jellies, iffy takeout leftovers, and plastic dial from thermostat).

Belch loud enough to wake wife or girlfriend. When she enters kitchen, bellow, “Can’t you see I’m working here?”

Fall asleep on kitchen floor.

After 4-5 more hours, wake up on subway, fully dressed from the waist up, drinking a Diet Snapple.

**The lysolipid is lysophosphatidylinositol, and we don’t know anything about it, except we’ve used phosphatidylinositol before in an ill-fated attempt to make dual-lamallelar liposomes in order to deliver a payload to a cell nucleus, one of the failed experiments that left us depressed and overwhelmed and so we left the lab bench. This was probably to the relief of many. So we are a little post-traumatic when we discuss membrane lipids.  One thing we liked about working at the lab was using liquid nitrogen, and so we sort of miss that because we’d drop all sorts of stuff in it, like our lunch. Very unprofessional, we know.  Another time we used regular marker instead of Sharpie and all our Eppendorf tube labels were wiped out by a leaky alcohol wash, and we had to figure out what we had by running everything out on a gel, and even then we weren’t sure.  But that doesn’t beat the person who used a squeeze bottle to run a path of methanol around someone’s chair and light the match, putting them in a ring of fire. Haha. Lawsuit. No, no one sued. But we always looked to see if the floor was dry.  Do not try this. Ever.

*** We learned that blood banks heat-treat the blood at around 120°F (or so), to kill the viruses yet keep the proteins intact. Hence, the jacuzzi. It seemed to work, but we didn’t run any controls, so who knows.