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Invisiblemicro
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How much lack of sleep can cause permanent pathology?
    #22412228 - 10/21/15 03:46 AM (8 years, 3 months ago)

I've looked this up and albeit unsettling I guess I fall into this small subset of cases that aren't affected so much.

Anyway, wasn't sure if anyone knew.

Anything I knew I could get that would work I would have tried...

I might try antihistamines; those help (esp. doxylamine) but only once and I have an interview here soon.

They don't help anymore unless I wait another week.


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Invisiblemicro
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Re: How much lack of sleep can cause permanent pathology? [Re: micro]
    #22412242 - 10/21/15 04:03 AM (8 years, 3 months ago)

Fuck, who am I kidding?

I'm not going to die and I'm not going to have permanent anything.

I'll get some doxylamine though, after I murder this coding problem.

(i don't know what they mean by decreased mental function. i wanna get shit done)



I'd delete the thread but that doesn't seem to work so mods feel free to if you want.


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OfflineLucisM
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Registered: 03/28/15
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Re: How much lack of sleep can cause permanent pathology? [Re: micro]
    #22412290 - 10/21/15 05:11 AM (8 years, 3 months ago)

Quote:

micro said:
(i don't know what they mean by decreased mental function. i wanna get shit done)





Arent you gay and use meth though, like all gay people I know always have shitloads of energy, well add that to the meth and you're the perfect storm.


I am probably totally wrong here, just a simple observation I have made.:lol:

I have slept 6 hours in 3 days, and am kinda tired, but sill have decent mental function.


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Invisiblemicro
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Re: How much lack of sleep can cause permanent pathology? [Re: Lucis]
    #22412301 - 10/21/15 05:30 AM (8 years, 3 months ago)

nah, coming off basically ghb

i think i slept saturday night but the week before had 5 nights, no sleep

still, it's a good thing right now

i need to do this stuff then go into doxylamine coma

whatever is left i don't care, as long as i don't look like a raccoon

final interview on fri


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OfflineLucisM
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Re: How much lack of sleep can cause permanent pathology? [Re: micro]
    #22412316 - 10/21/15 05:43 AM (8 years, 3 months ago)

I would think as you age lack of sleep would effect your health more, which makes sense.

I have noticed when I was in my 20's it was not bad to miss a day and rage hard, but nowadays I can feel it a lot more.  I think the kratom kinda numbs the sleep deprivations effects though, could be wrong.

Hope your interview goes well. :cheers:


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Invisiblemicro
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Re: How much lack of sleep can cause permanent pathology? [Re: Lucis]
    #22412335 - 10/21/15 06:09 AM (8 years, 3 months ago)

I'm an alcoholic; I go through it every time I stop drinking.

Just luckily this stuff I *can* quit easily and I'm not shaking in a corner.

Actually, I feel pretty good!

And 33 isn't THAT old =P

Well 34 in a week and some change >.>


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OfflineOggy
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Re: How much lack of sleep can cause permanent pathology? [Re: micro]
    #22419275 - 10/22/15 05:33 PM (8 years, 3 months ago)

I have severe insomnia and I haven't noticed any mental problems from it. I typically get around 4 hours of sleep every night, and after two weeks I crash hard and sleep for about 12-18 hours if I some how manage to stay asleep.

I use a lot of math for my hobbies though(programming/electrical engineering), maybe you could try brushing up on algebra?
And the only drug I use is cannabis. Which has ended up making my insomnia worse, for whatever reason.

[edit] I've had insomnia since I was a teenager, around 15 years now.


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Edited by Oggy (10/22/15 05:35 PM)


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Invisiblemicro
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Re: How much lack of sleep can cause permanent pathology? [Re: Oggy]
    #22428996 - 10/24/15 07:36 PM (8 years, 3 months ago)

i'm in engineering :V

algebra isn't brushing up but beating a dead horse

eh, i couldn't sleep 5 nights but now i am ok

job interview went well, I think


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OfflineKonyap

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Re: How much lack of sleep can cause permanent pathology? [Re: micro]
    #22437726 - 10/26/15 09:09 PM (8 years, 3 months ago)

anything past 24 hours is irreversable
your brain is like a muscle that's always on and even more awake when you're asleep becuase it's cleaning itself out


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OfflineYukon Cornelius
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Re: How much lack of sleep can cause permanent pathology? [Re: Konyap]
    #22437822 - 10/26/15 09:27 PM (8 years, 3 months ago)

Quote:

Konyap said:
anything past 24 hours is irreversable
your brain is like a muscle that's always on and even more awake when you're asleep becuase it's cleaning itself out




Nope... If you're going to make sweeping generalizations like that you need some extraordinary evidence.

If staying awake more than 24 hours causes irreversible brain damage every college student or self employed programmer I know is halfway to becoming a vegetable.

I'd suspect that over a week would be considered detrimental but not permanent, rats will die after two weeks of no sleep so that indicates there is a threshold somewhere.


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Edited by Yukon Cornelius (10/26/15 09:37 PM)


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OfflineKonyap

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Re: How much lack of sleep can cause permanent pathology? [Re: Yukon Cornelius]
    #22437899 - 10/26/15 09:41 PM (8 years, 3 months ago)



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OfflineYukon Cornelius
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Re: How much lack of sleep can cause permanent pathology? [Re: Konyap]
    #22438027 - 10/26/15 10:07 PM (8 years, 3 months ago)

Quote:

Konyap said:
english??
http://www.forbes.com/sites/melaniehaiken/2014/03/20/lack-of-sleep-kills-brain-cells-new-study-suggests/




Do you even science bro?

Key words from the abstract of the actual study and not the news article.

Quote:

Mice lacking SirT3 lose the adaptive antioxidant response and incur oxidative injury in LCns across brief wakefulness. When wakefulness is extended for longer durations in wild-type mice, SirT3 protein declines in LCns, while oxidative stress and acetylation of mitochondrial proteins, including electron transport chain complex I proteins, increase. In parallel with metabolic dyshomeostasis, apoptosis is activated and LCns are lost. This work identifies mitochondrial stress in LCns upon wakefulness, highlights an essential role for SirT3 activation in maintaining metabolic homeostasis in LCns across wakefulness, and demonstrates that extended wakefulness results in reduced SirT3 activity and, ultimately, degeneration of LCns.




Quote:

While it is difficult to discern whether the loss of LCns and injury of this magnitude are sufficient to result in cognitive impairments, we propose that repeated occurrences of Ext Wake (as is commonly observed in night shift workers) could result in a cumulative loss of LCns that would be sufficient to influence cognition and neurodegenerative processes, in predisposed individuals, as changes in SirT3, FoxO3a, and O2−· were evident in the majority of remaining LCns in Ext Wake.




They're actually locus coeruleus neurons, the article misspells the specific neurons they're writing about! :lol:

This is just a common case of hyperbole about an interesting publication that a journalist skims over and writes a provocative think-piece about.

I'm not saying lack of sleep is healthy, but one study regarding the specific effects of sleep deprivation on one type of neuron is not sufficient evidence to say that it causes completely permanent impairment of cognitive function in a health individual.


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OfflineKonyap

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Re: How much lack of sleep can cause permanent pathology? [Re: Yukon Cornelius]
    #22438058 - 10/26/15 10:15 PM (8 years, 3 months ago)



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OfflineYukon Cornelius
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Re: How much lack of sleep can cause permanent pathology? [Re: Konyap]
    #22438073 - 10/26/15 10:18 PM (8 years, 3 months ago)

Wow, you figured out how to post non-sequitur gifs instead of writing an actual response.

Great job! :thaaannks:


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Invisiblemicro
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Re: How much lack of sleep can cause permanent pathology? [Re: Yukon Cornelius]
    #22438717 - 10/27/15 02:23 AM (8 years, 3 months ago)

Yeah, I never got posts like that either.

I tend to ignore all articles in magazines that talk about killing brain cells.

I've been burned too many times.

The journal article was quite interesting, though.

I guess the idea is repeated cycles of extended wakefulness led to downregulation of SirT3 and translocation of FoxO3a which causes a downregulation in superoxide dismutase (I'd assume) in the LC in mice. This would accumulate O2- (the superoxide radical) that is generated in the LC during cellular respiration and is associated with acetylation of mitochondrial proteins due to imbalanced homeostasis, mainly redox.

All this was thought to lead to apoptosis (triggered cell death) in the LC. Since the wild-type SirT3 showed upregulation of SirT3 at first and the mutant types did not, it appears this plays a role in mitochondrial homeostasis. This causes less SirT3 and SOD2 and more oxidative stress, increased NAD+ etc. in the mutant types and after repeated long-term wakefulness in the wild-type mice. Age-related hearing loss caused by downregulation of SirT3 is thought to be from oxidative conditions as well, according to the article. That seems almost like a switch into reverse. Therefore, I think it is rather hard to infer any certain sequence of events leading to apoptosis.

From the article:

Quote:

It’s the first study to show (if only in animals) that sleep loss can lead to irreversible brain cell damage.




...wat? No, it causes oxidative stress leading to apoptosis. Without the later it is likely the neurons could recover, but there are reasons for apoptosis in conditions like this, i.e. to prevent mutations from propagating leading to things like cancer and genetic disease. There is no irreversible cell damage (at least from anything besides apoptosis resulting in cell death, of course) and the article states pretty clearly it is oxidation.

From the article, again:

Quote:

Researchers from the Center for Sleep and Circadian Neurobiology at the University of Pennsylvania found that prolonging wakefulness damages a particular type of brain cell called locus ceruleus (LC) neurons, which play an important role in keeping us alert and awake.




Despite it's connection with norepinephrine release and the raphe nuclei, hence serotonin, I still have no idea wth she is talking about. Where does it say that is helps "keep us alert and awake?" Those two words are not even in the article >.<

Regarding the LC:

Quote:

The projections of this nucleus reach far and wide. For example, they innervate the spinal cord, the brain stem, cerebellum, hypothalamus, the thalamic relay nuclei, the amygdala, the basal telencephalon, and the cortex. The norepinephrine from the LC has an excitatory effect on most of the brain, mediating arousal and priming the brain’s neurons to be activated by stimuli.

As an important homeostatic control center of the body, the locus coeruleus receives afferents from the hypothalamus. The cingulate gyrus and the amygdala also innervate the LC, allowing emotional pain and stressors to trigger noradrenergic responses. The cerebellum and afferents from the raphe nuclei also project to the LC, in particular the nucleus raphes pontis and nucleus raphes dorsalis.




So, according to Wikipedia, it is a regulatory hot-spot, receiving information from the hypothalamus. It is also involved in the response to stress and emotional pain, receiving info from the cingulate gyrus and the amygdala, so it can release noradrenaline. It is also associated with the raphe nuclei which releases serotonin (5HT).  Since NAD+ was elevated in this area for wild types at first according to the paper, could it have been a result of stress itself and not lack of sleep?

Having worked in medical research I know that mice are known to spontaneously die, especially when under stress in the laboratory. I have seen this happen in a wild mouse as well, outside a laboratory setting. Looking it up:

Quote:

Spontaneous mortality with unknown cause in adult and neonatal mice without prior reported illness was the most commonly reported issue, followed by dermatitis, ocular disease, and nonspecific clinical signs including lethargy, poor hair coat, and muscle wasting.




Ocular disease, if not directly affecting the eye, could be from the basal telencephalon going into the LC. It definitely seems there is marked pathology here in the LC.

I'm not quite sure if mice are the same in this regard, although SirT3 is mitochondrial and present in both rodents and people. Out of curiosity, I put the primers the article lists into a BLASTn query to get the mutants:

https://www.ncbi.nlm.nih.gov/nucleotide/354794941?report=genbank&log=nuclalign&blast_rank=3&RID=2Y6N441D01R

https://www.ncbi.nlm.nih.gov/nucleotide/354793809?report=genbank&log=nuclalign&blast_rank=4&RID=2Y6N441D01R

... and found out human DNA has similarities in chromosome 5:

https://www.ncbi.nlm.nih.gov/nucleotide/15281226?report=genbank&log=nuclalign&blast_rank=66&RID=2Y6N441D01R

Still, the article was only making a conjecture regarding the observed pathology in the LC. It was also a study on mice that shows a direct pathology in the stress part of the brain. People do not spontaneously die for no apparent reasons, but mice seem to, and IME, it happens much more frequently when stress is a factor. It even states:

Quote:

... found that disrupted circadian rhythms resulted in degeneration of LC brain cells and ultimately apoptosis.

...

The researchers limited the test mice to four to five hours of sleep over each 24-hour time period. After just three days of sleep deprivation the mice experienced a 25% loss of LCs in a particular section of the brain stem.




That seems a bit far fucking extreme for people, don't you think?

I've never heard of this causing problems in people but I've seen mice seppuku by telepathy.

It also claimed:

Quote:

the discovery that a protein called SirT3 (full name sirtuin type 3) protects LCs from the damage caused by lack of sleep




No, it helps regulate homeostasis but the article clearly said there was oxidation already present in part caused by translocation of FoxO3a and the resulting accumulation of superoxide radicals (and I believe it mentioned peroxidases as well). The rest was caused by a longer-term trend of a lack of SirT3 being generated when it should.

The upregulation in SirT3 was to STOP THIS initial oxidation and balance redox in the LC. Further lowering of expression of SirT3 would result in an imbalance in homeostasis incl. redox, as seen in the mutant types and extended cycles of no sleep in the wild types. The issue isn't that we need more of this but rather a series of interconnected events in mice.

Here she even tries to quote the article, including fucking quotation marks:

Quote:

“We now have evidence that sleep loss can lead to irreversible injury,” says lead author Sigrid Veasey, MD, associate professor of Medicine at the University of Pennsylvania’s Perelman School of Medicine. ”This might be in a simple animal but this suggests to us that we are going to have to look very carefully in humans.”




That isn't what he said... ANYWHERE in the article.

Here is EXACTLY what he said:

Importantly, Ext Wake is associated with a loss of LCns that occurs, at least in part, through apoptosis. The work shows, for the first time, that extended sleep loss is a metabolic stressor to LCns and that extended wakefulness can result in LCn loss.

Maybe I'm just being picky but there were never any results that showed anything regarding "irreversible injury." The body may trigger apoptosis to destroy the "bad" cells, but this is cell death. The damage was from an increase in ROS along with an imbalance maintaining homeostasis, especially in the mitochondria, where it is particularly problematic.

Looking at her other stuff though:

Quote:

Unusual sleep patterns, particularly sleeping during the day and staying up late at night, wreak havoc with the activity of your genes, new research shows.




NEWS FLASH: Now sleep loss can change your fucking DNA :o

NO, NO, NO. Gene expression (transcription) IS NOT DOING ANYTHING to your genetics.

Your genes are working fine; your body is upregulating or downregulating protein expression as it should be.

Quote:

Daytime sleeping disrupted the rhythms of up to one third of the participants’ genes.




NEWS FLASH: Your genetics also have circadian rhythms just like we do!

WOW, I never even knew genes went to sleep ^___________________^

Also, ONE THIRD? Of all 20 to 25 THOUSAND of them?!?!

How did they test all of them? :V

Wtf are rhythms of genes, anyway?

Quote:

Using a light-controlled sleep lab, Dijk and team manipulated the study participants’ sleep patterns, postponing their bedtime by four hours a day until the subjects were 12 hours out of sync with their normal day/night biological clock. The purpose was to mimic the effects of jet lag or working the night shift, the researchers said.




So getting 12 hours out of sync with your circadian rhythms can alter gene expression?

Enough to show in a sensitive blood panel?

This should really fall into the "no shit" category.

I'm sure eating a sandwich does, too.


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(Avatar is Maxxy, a character by Mizzyam, RIP)


Edited by micro (10/27/15 03:17 AM)


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