Glymphatic system clears toxins in the brain during sleep (2013) | Hacker News Reader

Glymphatic system clears toxins in the brain during sleep (2013)

urmc.rochester.edu

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Really interesting 3 part podcast with an MD and a neuroscientist sleep expert https://peterattiamd.com/matthewwalker1/

They dicsuss the glymphatic system's role in sleep, the many many detrimental effects of sleep too little sleep, the link between sleep and Alzheimer's, and all sorts of awesome stuff.

I actually got a sleep study and was diagnosed with sleep apnea after I listened to this episode and had the wits scared out of me about my sleep hygeine. :)

I was suffering from extreme daytime sleepiness that was impacting my job, and I got a sleep study and was told I didn't have sleep apnea and melatonin was suggested which didn't have a perceptible effect.

Even prior to that, for all of my adult life, my sleep habits had not been normal; I always felt like staying up longer and sleeping longer, and waking up for scheduled things was painful, but having commitments like work or appointments was the only way I could force myself to get up.

By accident, I found out my friend was taking bupropion, and I asked my doctor about it, and once I started taking it, my sleep cycle is practically normal. I have no idea why, but it was almost magical. Bupropion is sold as both a smoking cessation drug and an antidepressant, and it seems to do something to nicotinic receptors (of course) and to norepinephrine.

Edit: and caffeine never helped me; I only developed a tolerance and then when I stopped drinking coffee on weekends I would feel even worse than usual.

Something that really bothers me about coffee culture is that coffee is seen as a solution to being tired when really all it is is just an alertness booster. The main neurological cause of sleepiness is the brain’s desire to do memory optimization which can only happen by sleeping at the right time. Correct timing is really important and it seems to me like you have DSPS (delayed sleep phase syndrome). Most people’s circadian rhythms are a bit longer than 24 hours (usually between 24.5-25.5 hours) though external signals like exercise or bright light in the morning reset it to being closer to 24. If you have DSPS, yours isn’t reset well (you can try the aformtentioned morning bright light and exercise to change this) and you have a tendency to wake up later and later each day. The problem is that if you have to wake up at 7 every day and you think you need 9 hours of sleep you’ll try to sleep at 10 to get enough which backfires. The reason it can backfire is that for good sleep you need both strong homeostatic sleep signals (tiredness from thinking a lot or doing a lot of effort in the day) and circadian (sleepiness goes and comes cyclically). If you sleep at 10 and have DSPS, even if your homeostatic signals sleep, it is likely that your circadian isn’t which means you end up tossing and turning throughout the night. If you slept maybe an hour later you’d get full circadian and homeostatic sleepiness giving you good quality sleep but if you have to wake up at 7 you have to cut short sleep with an alarm clock which isn’t great since your brain can’t complete all the memory optimization it wants. I would say though that sleeping later more restfully for shorter will do you better than sleeping earlier restlessly. (Sorry for the essay, sleep is something I care about a lot. I hope this was a little helpful.)

From experience, DSPS (delayed sleep phase syndrome - the blanket term for what you describe) is terrible to have. I have found that most people I discuss it with who have normal sleep cycles will staunchly refuse to consider that such a thing could possibly exist. "Have you just tried going to bed earlier?" (wow, never thought of that thanks), "You just need to form a good sleep habbit", "You're just lazy", "Stop making excuses", "Just try harder" etc. - pretty much the same as telling a depressed person to "just be happy"...

Having had a look, that's really interesting that Bupropion helped, since it seems to quite commonly cause insomnia as a side effect. What kind of dose is that?

Half the typical daily total amount used for smoking cessation or depression. I tried a step up of about 1/3rd, and felt ill, so I went back to the initial amount.

Incidentally, I read just now that it's used for ADHD off-label.

Sudden sleepiness/fatigue is a symptom of benign brain tumors. You should get an MRI scan.

It wasn't really that sudden or novel. It was a tendency I had to varying degree since high school, and it became worse as my motivation decreased.

But the notable thing is that given how long standing it was, it was really amazing to me that I now feel like 7-8 hours of sleep is enough, just like a switch was flipped.

Bupropion is also an antidepressant and fatigue is a symptom of depression.

Sometimes after sleeping, especially after a good night's sleep, I have a feeling that my brain has been scrubbed clean. It physically feels "fresh", similar to the feeling of having brushed my teeth. Not totally sure if it's not just my imagination, but I like to think there's some science behind it :)

I can't say the same, but conversely if I have poor quality sleep characterized by too much dreaming, the next day I'll wake up with a feeling that's best described as a light burning sensation in my head. It's not painful, just unpleasant.

I've often theorized it's due to the glymphatic system being unable to perform its job properly the previous night. I've noticed anything that impairs sleep will do this: from failing to take my usual magnesium supplement before bed, to alcohol, to the incorrect ratio and dose of cannabinoids.

Poor quality sleep: burning head sensation plus usual tiredness.

Good quality sleep: wake up feeling great. Sadly no "clean" sensation, however. That does sound interesting. :)

It's worth noting duration doesn't matter. I can have 4 hours of quality sleep and just be tired sans any burning sensation, or 8 hours of poor quality sleep and wake up with it. Definitely weird.

If I sleep really long I get a buzz in my head. I've never done drugs, but it kind of feels like what I think being high would be. Sort of like a brain-orgasm.

It feels really good for about 4 hours, then disperses.

I am assuming "never done illegal drugs" is probably what you mean.

Does this "waste" accumulate indefinitely if you are constantly lacking sleep, or does it get flushed out in full every night you get a good night's sleep? So say I had a crappy sleep schedule for 3 days, but on the 4th day I slept a lot and feel very rested. Did the last night's cleaning take care of all the accumulated waste?

Articles and studies I've seen suggest that it takes more than one night to get caught up and that some things become seriously intractable if you are routinely short of sleep.

That's interesting, I wonder if this harvard study on "catching up on sleep" accidentally shows in some way how much sleep is required to flush out the toxins? They stated, "10-hour sleep opportunities consistently restored vigilance task performance during the first several hours of wakefulness."

https://stm.sciencemag.org/content/2/14/14ra3.abstract

I looked at the link. They actually were also having people stay up longer, so I don't think you can conclude that.

The brain also "resets" during sleep. As part of that process, it shrinks substantially.

Aa you do stuff during the day, synapses swell as they see repetitive use of the same pathways. This reinforces those ideas or actions, crowding out other things. In order to restore short term memory formation and the ability to learn new things, your brain has to reset at night.

There's also interesting research on two proteins, amyloid and tau, that accumulate faster when people are sleep deprived. They are both associated with Alzheimer's.

One of them rapidly resolves when you get caught up on sleep again. The other doesn't.

Do you have any references for synapses changing size with use? A quick google indicates the opposite, if anything:

http://blogs.discovermagazine.com/neuroskeptic/2015/06/08/br...

Brain expansion (not contraction) overnight is unexplained, but may be due to fluid retention. That definitely affects the spine - causing us to be slightly taller and less flexible in the morning.

Striking electron microscope pictures from inside the brains of mice suggest what happens in our own brain every day: Our synapses – the junctions between nerve cells – grow strong and large during the stimulation of daytime, then shrink by nearly 20 percent while we sleep, creating room for more growth and learning the next day.

https://neurosciencenews.com/sleep-brain-reset-6047/

Sleep Shrinks the Brain--and That's a Good Thing

Without a nighttime reset, synapses could burn out like an outlet with too many appliances plugged in

https://www.scientificamerican.com/article/sleep-shrinks-the...

The sleeping and the anesthetized mice had a 60% increase in the volume of fluid, apparently because brain cells actually shrink to allow more space in the channels. When the researchers woke the mice up, the flow of fluid into the brain abruptly slowed.

http://m.nautil.us/blog/sleep-when-brain-cells-shrink--neuro...

Interesting, thanks.

I imagine there are second-order effects of sustained e.g. amyloid saturation.

Sleeping on one's right side can exacerbate acid reflux (which can increase your risk for throat / esophageal cancer).

So, taken together with this, sleeping on the left side seems ideal.

My grandma* used to say: After an evening meal, go to sleep on your left side; if you wake up from bad dreams, turn to right side and sleep till dawn/morning.

* she died 23yrs ago.

Particularly if you suffer from diverticulitis as I do, putting pressure on the left side seems to lessen or calm spasms.

Most diverticulitis occurs on the left side in the West and the right side in the East.

Really? I thought the lower sigmoid colon was in the same place on everyone. Does that mean some other part of the digestive tract is stressed to the point of forming diverticulae in an Eastern diet?

I've got a hiatal hernia which makes this even worse. What I've found is that I can sleep fine on my right side as long as my stomach has cleared, which usually takes about 3 or 4 hours.

sleeping on the left can directly put pressure on the heart.

To maximize glymphatic toxin clearing the lateral sleeping position is currently recommended.

1. https://neurosciencenews.com/lateral-sleep-position-neurolog...

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524974/

This study was done on anesthetized rodents. In conversation I've heard support for sleeping on one's side (laterally).

This doesn't suit me physically. My shoulders are too wide. I twist into horrible positions and hurt the following morning.

That’s the side position. Lucky for me I sleep that way to make my head comfortable. I wonder if it is more refreshing to sleep that way too then?

If I sleep anywhere but my side, my throat tries it’s darndest to choke me to death, on behalf of the sleep apnea. So it works great for me!

Myself and all my three children from birth have been belly sleepers. Never slept a wink until they could turn themselves over since they make you put them on their backs. Always thought it odd.

The position shown in the first link will eventually fuck up the shoulder though. Aim your arms downward if you're having shoulder problems.

Any evidence to support this? A downward facing arm tends to be more internally rotated due to the weight on it, which is definitely a more prone position.

If a fucked up left shoulder counts as "evidence", sure. :-)

Doctor prescribed an MRI and then suggested a surgery (with a minimum of 6 months of recovery). I declined. Turns out it was my sleeping position. I used to sleep pretty much exactly as shown, except towards the morning my arm would also go under the pillow, further straining the shoulder. Now when I sleep I extend the arm slightly downwards. This was sufficient to eliminate symptoms.

Obviously this will vary based on anatomy. Do a simple experiment. Lay down in this position and see if you have tension in the shoulder joint. If you're muscular (I am), you will very likely feel it. That tension, applied 8 hours each night, will most definitely cause issues.

ya it looks like potential tendon impingement/bursitis to me.

Isn't that considered not as good for one's heart? I thought lying on the back is best for heart health?

roll to the right - ok; roll to the left, pressure on the heart.

But sleeping on right apparently aggravates heartburn. (Is there some law of advice, that there is always equal and opposite advice?)

https://www.nytimes.com/2010/10/26/health/26really.html

The downsides of having organs all over :). Any position might either stress the organs that end up on the bottom or encourage a less that ideal flow of fluids.

I guess YMMV. Some trial and error may be needed to see what works for you even if the theory says otherwise (heartburn is an easy one to spot).

I find myself sleeping in bellydown position.

I am not an expert, so I might be missing something, but is this related to the finding that was reported in 2014 [1]? Is it the new development that now they have actually observed the glymphatic system at work?

[1] [https://www.nytimes.com/2014/01/12/opinion/sunday/goodnight-...

I've believed this to be true for a while now, as I've gotten older this has gotten obvious to me.

When you're younger everything works so well you don't notice the subtle differences often times. But as I've rounded 40 I've realized just how big a difference good sleep can make.

After having three concussions in the past two years, one just recently—I've taken a keen interest in learning as much as I can about mild traumatic brain injury (mTBI).

Impairment of glial-lymphatic function is thought to play a role in all manner of neurodegenerative disease, including TBI and mTBI.[0][1][2]

My potentially incorrect layperson oversimplification:

mTBI in particular is broadly characterized as a loss of homeostasis within the brain, more specifically metabolic dysregulation secondary to primary mechanical injury. When you suffer a concussion, an inflammatory response occurs within the brain. This is useful in the acute phase of injury, but can lead to chronic neuroinflammation if not properly mediated. Oxidative stress secondary to the primary injury can interfere with this process, and what you end up with is a complex biochemical cascade that furthers metabolic dysregulation and loss of homeostasis, resulting in latent neurodegeneration (brain damage). Among those systems impacted by said dysregulation is the glymphatic system.

Traumatic Brain Injury (TBI) by contrast is a term used to describe brain injury more severe than that of a simple concussion. It's basically everything mTBI is and then some: compromised blood–brain barrier, immune cell infiltration, necrosis, sometimes direct mechanical destruction of brain tissue in the case of open head injuries. It's typically quite horrific.

In researching the topic, I've noticed many papers suggest pathologies from Alzheimer's and Parkinson's to CTE may in fact stem from chronic loss of [metabolic] homeostasis within the brain. Whether that's from chronically poor sleep, or hits to your head, the end result is disturbingly similar.

In my own experience, the number one thing that has helped me recover after a concussion has been sleep. Usually following an injury I need more of it than normal. It's not hard to imagine the glymphatic system plays a critical role in healing.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261373/

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034172/

[2] https://www.ncbi.nlm.nih.gov/pubmed/28859995

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