"Astrocytes Regulate Daily Rhythms in the Suprachiasmatic Nucleus..." [Dysfunction delays sleep.]

[ZeroGravitas]

Delayed sleep phase and non-24-hour circadian rhythm have been a major problem in my life since my teenage years, over a decade before recognising my gradual onset CFS/ME symptoms as such...

So this article, posted here on to Reddit really caught my attention, seeing as there has been a lot of interest on this forum (and elsewhere) in microglia inflammation in the CNS (and stopping it from) probably causing our brain fog and other problems. (@Hip seems to have written the most, e.g. "Chronic Microglial Activation in ME/CFS, And Its Possible Treatment Using Microglial Inhibitors", and probably has more recent info.)

I'd assumed these symptoms of mine to be linked, but perhaps assumed something like (microglia mediated) neuro-inflammation in the hypothalamus was knocking out signalling/resetting of the SCN's timing, or it caused permanent damage to the tiny cluster of neurons (somewhat like the wakefulness promoting, orexin secreting neurons being greatly diminished in narcolepsy)... But this work seems to be showing that astro-glia (astrocytes) are required to contribute, themselves, to correct pacemaker rhythms. A more direct connection.

So I'm wondering: if their dysfunction/alteration can directly cause my kind of 25h sleep cycle problems (now up to 26h), and this is a common factor with the cause of my CFS, then why is this rotating sleep/wake cycle not even more common in other pwCFS/ME, in general? I mean, sleep difficulties are super-common, but it's: difficulty getting enough, or deep enough, and napping during the day and being generally messed up, wired and tired, etc, rather than specifically delayed (and too much) like me.

From the article: https://source.wustl.edu/2017/03/clock-stars-astrocytes-keep-daily-time-brain-behavior/

Asked to define the body’s master clock, biologists would say it is two small spheres — the suprachiasmatic nuclei, or SCN — in the brain that consist of 20,000 neurons. They likely wouldn’t even mention the 6,000 astroglia mixed in with the neurons, said Erik Herzog, a neuroscientist in Arts & Sciences at Washington University in St. Louis. In a March 23 advance online publication from Current Biology, Herzog and his collaborators show that the astroglia help to set the pace of the SCN to schedule a mouse’s day.
[...]
“When we deleted the gene [Bmal1] in the astrocytes, we had good reason to predict the rhythm would remain unchanged,” Tso said. “When people deleted this clock gene in neurons, the animals completely lost rhythm, which suggests that the neurons are necessary to sustain a daily rhythm.”

Instead, when astrocyte clock was deleted, the SCN clock ran slower. The mice climbed into their wheels one hour later than usual every day.

Paper's Summary: http://www.cell.com/current-biology/abstract/S0960-9822(17)30205-1

Highlights

• •Astrocytes, like neurons, are synchronous circadian oscillators in the SCN
• •SCN astrocytes modulate daily rhythms in locomotor behavior and SCN physiology
• •Loss of Bmal1 in SCN astrocytes lengthens period in SCN neurons and behavior
• •The circadian period of the SCN and locomotion depends on astrocyte period

Summary
Astrocytes are active partners in neural information processing [ 1, 2 ]. However, the roles of astrocytes in regulating behavior remain unclear [ 3, 4 ]. Because astrocytes have persistent circadian clock gene expression and ATP release in vitro [ 5–8 ], we hypothesized that they regulate daily rhythms in neurons and behavior. Here, we demonstrated that daily rhythms in astrocytes within the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), determine the period of wheel-running activity. Ablating the essential clock gene Bmal1 specifically in SCN astrocytes lengthened the circadian period of clock gene expression in the SCN and in locomotor behavior. Similarly, excision of the short-period CK1ε tau mutation specifically from SCN astrocytes resulted in lengthened rhythms in the SCN and behavior. These results indicate that astrocytes within the SCN communicate to neurons to determine circadian rhythms in physiology and in rest activity.

 

[Tunguska]

Seems like a double-whammy as to why glucocorticoids might help

 

[NelliePledge]

Hi Z. I struggle to get my head round the science. My sleep problem is timing I regularly am awake at 3 am and my day only gets going at lunchtime. I take amitriptyline which can help me get to sleep sooner 1am if lucky but isn't that reliable also I think it gives me bad dreams sometimes. I thought this sort of delayed sleep pattern was fairly common.
N

 

[MeSci]

Hi Z. I struggle to get my head round the science. My sleep problem is timing I regularly am awake at 3 am and my day only gets going at lunchtime. I take amitriptyline which can help me get to sleep sooner 1am if lucky but isn't that reliable also I think it gives me bad dreams sometimes. I thought this sort of delayed sleep pattern was fairly common.
N

I think I've heard quite often of people's cycles being typically longer than 24 hours.

Also, I don't think other species tell us much about humans (having studied them both, mostly the latter on realising that fact).