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The sleep switch: hypothalamic control of sleep and wakefulness

Discussion in 'Other Health News and Research' started by heapsreal, Nov 10, 2011.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    More than 70 years ago, von Economo predicted a wake-promoting area in the posterior hypothalamus and a sleep-promoting region in the preoptic area. Recent studies have dramatically confirmed these predictions. The ventrolateral preoptic nucleus contains GABAergic and galaninergic neurons that are active during sleep and are necessary for normal sleep. The posterior lateral hypothalamus contains orexin/hypocretin neurons that are crucial for maintaining normal wakefulness. A model is proposed in which wake- and sleep-promoting neurons inhibit each other, which results in stable wakefulness and sleep. Disruption of wake- or sleep-promoting pathways results in behavioral state instability.The relationship between sleep and wakefulness may depend on the balance of activity in the GABA/galaninergic systems and orexin/hypercretin systems of the posterior hypothalamus.

    http://www.cell.com/trends/neurosciences/abstract/S0166-2236(00)02002-6
     
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    http://www.psychology.uiowa.edu/faculty/blumberg/course_docs/seminar.2008/readings/mignot.2002.pdf

    An encephalitis epidemic in 1918-1926, the hypothalamus was recognised to be the problem of major sleep problems in these people. I wonder if it was an ME outbreak. Other articles i have read have mention the hypothalamus being injured in me/cfs patients. A specific part of the hypoth was injured, maybe this is the part of the brain injured in cfs/me that have sleep problems. people that dont have sleep issues didnt have an injury to this part, probably other parts of the hypothal?? interesting.

    cheers!!!
     
  3. August59

    August59 Daughters High School Graduation

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    The orexin/hypocretin are associated with narcolepsy. It's now considered an autoimmune disease due to the body attacking and destroying the orexin/hypocretins. It seems like our pituitary/hypothalmus region of the brain just takes a beating somehow.
     
  4. Enid

    Enid Senior Member

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    Very interesting heaps - the hypothalamus (some insult) is involved in all ME models I've seen. And from personal experience the use of GABApentin to full epileptic dose was the only thing that gave me deep sleep at last during that stage. Apparent Narcolepsy (tendancy to fall asleep) off and on previously, with hindsight, I suspect was not giving/allowing the deep sleep stage.
     
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Thats interesting Enid, What dose of gabapentin do you take?

    I normally use 600mg at night for leg pains/RLS, i have taken 1200mg before, but normally use a number of different things to get sleep, its my never ending problem.

    cheers!!!
     
  6. Enid

    Enid Senior Member

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    Just looking at a packet still here heaps I see it says - Epilepsy usual dose between 900mg and 2400mg daily. Mine were 100mg times 3 daily. I doubled at that awful stage for a period instinctively knowing that far from being simply pain relief it was affecting(aiding) sleep patterns. So I guess 600mg was my top dose over probably 2 months. I'm personally convinced that the deep sleep stage is what is severely disrupted in ME. Now it seems to come more normally and sleep more refreshing - no sleep aids needed (and even a glass of red wine with dinner goes down well !). It does take time but the sudden switches to full alertness out of the blue have disappeared too. Hope you can the way to improve your own sleep patterns heaps.

    (I may be looking at a late prescription box and the earlier ones much higher dosage - come to think of it, they were 300mg or 400mg times 3 daily at one stage or I took up to - the dose to allow deep refreshing sleep and healing one felt)
     
  7. merylg

    merylg Senior Member

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    This is interesting regarding Narcolepsy being found to be an Autoimmune condition due to a genetic mutation that causes T cells to attack and destroy Hypocretin:

    "For a long time, people have suspected narcolepsy had something to do with the immune system that it was killing cells that produce hypocretin," said Mignot, a professor of psychiatry and behavioral sciences and director of Stanford's Center for Narcolepsy. "But there hasn't been direct proof."

    During this study, the researchers ran whole-genome scans which allow for the analysis of hundreds of thousands of genetic variations of 1,800 people carrying the same HLA gene variant. Of the group, 800 had narcolepsy, and the goal was to find what differentiated these people from control subjects. The team found that a specific variation of a gene belonging to T cells specialized immune cells that play a role in all immune responses was present in narcolepsy.

    Because T cells are involved, Mignot believes the mechanism behind narcolepsy stems from the immune system. "Our discovery clearly shows narcolepsy is an autoimmune disease," he said.

    "This is a very important finding," said Merrill Mitler, PhD, a sleep disorders expert and program director at the National Institute of Neurological Disorders and Stroke, who was not involved in the study. "It puts in place another piece of the puzzle and shows a way to link [this gene variant] to hypocretin-containing neurons via an autoimmune attack."

    Mignot said it's likely that HLA and this T cell variant interact in a way that kills hypocretin cells. How exactly this interaction is triggered is not yet known, and he said future studies will focus on solving this mystery. Once more details emerge, he said, scientists may be able to identify people who are predisposed to narcolepsy and block specific gene variants in that person to stop the development of the disease.

    In the meantime, Mignot expects the findings to aid researchers studying other autoimmune diseases. No other autoimmune disease has shown an association with this specific T cell gene, he noted.

    "I'm sure immunologists are going to be very excited," said Mignot of the findings. "If we can work out what happens specifically in patients with narcolepsy, we'll be able to better understand the role of T cells in other autoimmune diseases that are more complicated and difficult to detect."

    http://www.eurekalert.org/pub_releases/2009-05/sumc-nia042809.php
     
  8. taniaaust1

    taniaaust1

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    thanks heaps and everyone else who found a shared info here. All very interesting.
     
  9. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Narcoleptics fall asleep though, i say this as its 2am and i have had 3 hours of medicated sleep. I wonder if antibodies attack something else when u cant fall asleep as in insomnia??
    After reading up on narcolepsy, it seems they can fall asleep but sleep isnt refreshing, but seems different to cfs sleep dysfunction. Maybe the autoimmune side of things is different in primary insomnia??
     
  10. Enid

    Enid Senior Member

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    I do agree heapsreal - the long bouts of seemingly narcolepsy before serious ME set in just left me feeling even more tired afterwards - unrefreshed - not the usual pattern of sleep stages.
     
  11. kaffiend

    kaffiend Senior Member

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    I often think that the extent of damage to neurons and nuclei within the hypothalamus can account for most of the symptoms of ME/CFS and the variability across individuals.

    Its functions are so well studied in animals (mice) through lesioning out specific nuclei and observing the effects. We DO currently have a lot of the answers to understand this disease, they're just spread out and it seems that clinicians don't concern themselves very much with mechanisms.
     
  12. merylg

    merylg Senior Member

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    You guys inspired me to give my (Rheumy prescribed) Gabapentin another go, to help with sleep. I took only 100mg at night and found it gave me a deeper, more satisfying sleep than I have had for weeks.
    Only drawback so far is a bit of drowsiness in the morning...so harder to "wake-up" and be alert.
    Bit worried about 2 things with Gabapentin...possible weight gain & possible build up of the drug in your system.
    (Though usually prescribed to help with neuropathic pain & to lower seizure threshhold it has some use in treatment of insomnia, OCD, social anxiety disorder and treatment resistant depression)

    http://en.wikipedia.org/wiki/Gabapentin
     
  13. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I think our bodies/brain likes to be dysfunctional, when we find something that helps and moves us towards being functional it go's whacky. Its good to revist past treatments as they can work again for awhile and then we need to revisit something else.

    I was having some good results with low doses of progesterone cream for sleep, it was improving my sleep quality alot, but of late it hasnt been doing the job. So im going to stop it for awhile and revisit it later. Forever chasing our tails.

    I find neurontin good for leg pain/RLS with minimal side effects.

    cheers!!!
     
  14. August59

    August59 Daughters High School Graduation

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    Heaps - I'm narcoleptic and i assure you I don't sleep good at night. I believe the thought used to be that our nightime sleep was so bad that we were very sleepy during the day and that still seems to be true, but the cause is different now in the fact that we lack hypocretin/orexin hormones. We end up with a randomized sleep pattern controlled by by who knows what? Melatonin? My neurologist says they still don't know, but they are suppose to be working on a synthetic or natural replacement for the hypocretin which is years away.

    Meanwhile, we are stuck with medical control. Most narcoleptics are on strong sleep meds (more and more going to Xyrem) and usually a stimulant during the day being anything from Provigil to Adderall. There are some doctors that will prescribe Desoxyn, which is the legal form of "meth".

    Then there is the "cataplexy" symptom to go with narcolepsy. I can't imagine to start laughing and then temporarily being paralyzed.
     
  15. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Hi August, my post wasnt meant to be offense towards narcoleptics(which i dont know alot about), just comparison of myself who doesnt sleep without meds and is there much of a difference in the narcoleptics who have poor sleep quality, is the cause of sleep problem that different or a small variation?? If u took away the cataplexy, it looks alot like someone with me/cfs who has severe pots/oi, maybe more in common then we realise. Its said that people with fibro have poor sleep quality as well, so i wonder what makes there condition different to narcolepsy. I wonder what makes us all slightly different ie insomniac, narcoleptic, fibro etc, is the cause in a different part of the brain maybe??? One day i hope they have it worked out cause im sick of taking sleep meds and my biggest fear is not being able to get sleep meds, my quality of life would deteriorate badly without them.

    Hypocretin/orexin looks interesting, i wonder if when a drug for this is available that non narcoleptics will be able to use it.
    Heres a link to Hypocretin/orexin, sleep and narcolepsy i found interesting http://med.stanford.edu/school/Psychiatry/narcolepsy/articles/bioessays23.pdf

    cheers!!!
     
  16. mellster

    mellster Marco

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    Here in CA some people use finest Indica right before bed (or some Sativa couple of hours before) and report that they sleep fairly well :) Any chance of legalization in Aussie-land soon?
     
  17. August59

    August59 Daughters High School Graduation

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    Dude, you know I wouldn't take anything from you offensive! I should of worded it a little differently.
     
  18. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    cheers!! dude.
     
  19. ty98

    ty98

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    Just started to try modafinil (provigil). My neurologist who specialized in cerebralu vascular has seen two of my brain MRIs and believes there could be some issue with my hippocampus. He really does not know that it will help, but having just tried it this week, it is making some small improvements. I ve been fighting problems for 4 years. Time will tell if this med will make improvements or not.
     
  20. ty98

    ty98

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    OK, I am taking this off the list of helpful supplements. I started Modafinil which seemed to have some benefits, but shortly after made things worse. I stuck with it for 4 rough days and decided it was not working. It had some bad mental effects and made me feel more ill.
     

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