Clues into PFS insomnia? Effects of SRD5A1 expression on sleep in socially isolated mice

Maybe this is piece of the puzzle. If this is already known then my apologies.

The following is from a paper showing a Japanese traditional medicine alleviates insomnia and increases sleep duration via ALLO production through upregulation of SRD5A1 in the olfactory bulb.

Abstract

Yokukansankachimpihange (YKSCH), a traditional Japanese medicine composed of 9 crude drugs, is designed to improve neurosis, insomnia in adults, and night crying in children.

YKSCH has been reported to improve diurnal rhythm in patients with Alzheimer’s disease and prolong the total sleeping time in healthy subjects. However, little is known about how YKSCH alleviates sleep disorders. Here, we investigated whether and how YKSCH treatment affected sleep latency and duration in group-housed and socially isolated mice.

Male ddy mice were treated with YKSCH [1,500 mg/kg, per os (p.o.)] in group-housed or socially isolated conditions for 3–4 weeks. After the last injection, mice were intraperitoneally (i.p.) administered with pentobarbital (60 mg/kg) and the sleep latency and duration was evaluated. The results show that pretreatment with YKSCH had no effect on sleep latency or duration in group-housed mice. However, YKSCH treatment significantly improved the reduced sleep duration in socially isolated mice. This effect of YKSCH was inhibited by the administration of bicuculline (3 mg/kg, i.p.), a GABAA receptor antagonist. Furthermore, we showed that YKSCH treatment improved the decrease in allopregnanolone content and its synthase expression levels in the olfactory bulb. These results suggest that YKSCH treatment improved social isolation stress-induced insomnia via the GABAergic pathway and that the mechanism of action of YKSCH is partly due to improvement of allopregnanolone levels of expression.

Several reports have shown that social isolation stress-induced behavioral abnormalities are related to the reduction in ALLO contents in the OB and PFC (22). The ALLO content is reported to be about twice higher in the OB than that in PFC (22). Olfactory dysfunction is frequently observed in patients with REM sleep behavior disorders, such as dementia and Parkinson’s disease (34, 35). In addition, some reports have shown that olfactory bulbectomy in rats induces a reduction in REM sleep duration and frequency (36). These reports suggest that the OB has an important role in sleep-wakefulness patterns. Biosynthesis of ALLO in the brain is regulated by two specific enzymes. It starts with the conversion of progesterone into 5α-dihydroprogesterone by the SRD5A1 enzyme. Next, 5α-dihydroprogesterone is converted into ALLO by the 3α-HSD enzyme. Social isolation stress does not change the brain’s content of progesterone and pregnenolone (29). In socially isolated mice, brain expression of SRD5A1 mRNA and protein was approximately 50% less than in group-housed mice, whereas the expression of 3α-HSD mRNA was unchanged (19). These reports suggest SRD5A1 is the enzyme responsible for producing the brain ALLO in this model. Here, we demonstrated that YKSCH treatment inhibited the decrease in both ALLO content and SRD5A1 expression levels in the OB

Brain cells synthesize ALLO from progesterone by two types enzymes, SRD5A1 and 3α-hydroxysteroid oxidoreductase. In socially isolated mice, the expression level of SRD5A1 is reduced in the OB and PFC, but 3α-hydroxysteroid oxidoreductase is unaffected (19). This report indicates that SRD5A1 is responsible for producing ALLO in this model. In this study, we investigated whether YKSCH treatment affected the SRD5A1 expression level in the OB and PFC. As a result, YKSCH treatment improved the reduction of SRD5A1 expression levels in the OB.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026005/

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Looool…I was really just looking into this compound 1 hour ago, and i was gonna post something about it (I was like 100% sure, that noone ever came to this :D, but you were faster than me ;D )…
Actually i was looking for a compound that would function as a HT1a partial agonist, and one of the plants in yokukansan contains it (Geissoschizine methyl ether, in Uncaria hook)…
Anyone ever tried this medicine before, or lives in europe and know how to get it?..Yokukansan

Edit: I remember that we have a japanese memeber in this forum, maybe he can give us some more information, if anyone can contact him, or give me his name

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@simonsayss

Haha. I guess I am not the only one who looks up buzzwords on google scholar from time to time.

YKSCH being a combination of 9 different herbs is a lot of homework to pore over to assess for any risk that could happen to us. And then each of these herbs are a multitude of different plant compounds that could help or harm us, e.g. beta-sitosterol. Not to mention any potentially negative entourage effects notwithstanding SRD5A1 upregulation. I mean, it’s herbs, right. Specificity of action is our best friend. Different brands of tribulus have caused persistent serious harm for some of us.
I am just too tired to go through all the literature right now.

I’ve been cycling Mediherb tribulus again (along with taking butyrate and tributyrin) and the tribulus indeed gives me constipation yet improves my sleep dramatically albeit at least for the time being.

That said, anyone brave enough to try this? lol. Here’s one vendor that has it on rakuten, seems there are many: https://global.rakuten.com/en/store/kenkoex/item/1220-4987045049934/

Hope some of our Japanese speaking friends could chime in though if they’ve tried this.
@Mr.Children
@synetic

To be honest, i dont even believe in doing all that research…There are no way in heaven that we can know, if a sepcific something might cause our condition to get worse…I have seen it all…From ppl getting better on Finasteride itself, to getting screwed up on Tribulus, to end up crashing eating salmon!!!..
There is no way except for trying…Even if there is solid research about something, and most probably might make us worse, or better, we can never really tell (Take TRT for example, low T, more must help, but NOOOOO!), since we clearly have completely different, and unexplained chnages in our body (FFS i cant even seem to put my hand on this curse…HOW???)…
Either way, i wasnt really looking for any plant as a matter of fact…I was somehow intrigued by looking for a compound that would act as a partial agonist on HT1a receptors (I know i have PFS, and this was never proven in PSSD, but at this point, i will accept the help of psychics if they give me any hope)…
I have found that Uncaria rhynchophylla, contains the compound im looking at…Problem is, there is no standarized extrakt, or Tincture of this plant, so i will have to go with my gut, and experiment…Wish me luck guys…Again! :smiley:

Interesting.
Last time I was in the sleep lab the doctor looked at me with big eyes as I had 0 minutes of REM sleep. Would be interesting to see the sleep pattern before and with the herb. The only thing I fear would be longterm stuff.

There is a Japanese-language forum here:

https://forum.propeciahelp.com/search?q=japanese%20forum

Click on the “globe” icon in each post for a translation.

I checked the link. It’s also available at Oriental Clinic in Korea, but you need clear clinical evidence to get the prescription. There is a way to buy from the online market in Japan and I have to investigate whether the customs office will allow this.

hey bro.One of Japanese users here is me.
I possibly can buy this medicine.(This doesn’t need prescription,so easily can buy on the internet)
But my symptoms are getting better,so I am afraid to try,tbh.
I think it is worth trying though…

Is it supposed to be a safe medication for the general public?..ofc for us even breathing might be dangerous but I’m talking generally speaking

if you’re getting better don’t. leave it to the fellas who are more severe

Forgot to highlight the fact that “SRD5A1 is the enzyme responsible for producing brain allopregnanolone in this model.” Wish more people would look into this.

Some other things that increase SRD5A1 (which includes toxins and finasteride itself lol):

Unfortunately the part about substances that increase SRD5A1 gene activity is so far blank.

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This makes sense from what I’ve read.

I believe studies have showned decreased Allo amongst other neurosteroids in PFS patients.

Melcangi’s latest study also is going to administer Allo directly into rats who have been given PFS.

Also, some find relief from things like L-theanine and glutamine, which I think boosts production of Allo and regulates GABA in the brain.

Again, how can Melcangi say that they have ‘PFS’? If they don’t have PFS the entire undertaking is futile.

This is a relevant question. Obviously, I’m not the most equipped to answer it here.

I do agree that it seems that Melcangi doesn’t have a clear definition of the underlying mechanisms of PFS.

Instead, I assume he’s going to have a group of rats that are “healthy” and a second group who have been administered heavy/long doses of finasteride.

It is the expectation/assumption that there will be significant differences between the two groups in the following categories

  • Neurosteroids
  • Neurotransmitters
  • Intestinal population
  • Analysis of gene expression

**Although this might not give us the underlying mechanism of PFS, it will still be the most comprehensive analysis of changes that PFS sufferers are going through. **

In addition, he will see if the proposed changes benefit from the administration of ALLO, which is, as far as I understand, will be the first ever proposed medical treatment for PFS, or at least the observable cascading side-effects of PFS.

If the experiment produces succesful results, then I’m speculating we have a pathway to administer the same treatment on ourselves & reap the benefits by the following:

  1. checking for the same markers from Melcangi’s proposed “PFS” model. I don’t know if it will be feasible for us to have our gene expression & microbiome population examined?

  2. if the PFS patient’s markers are matching to Melcangi’s “PFS” model, then we could administer ALLO to ourselves.

Who here would turn down even a marginal improvement in their symptoms, even if it’s not directly tackling the underlying mechanism of PFS? Moreso, if that improvement is coming through a well-documented scientific study.

And I’m sure this will not be Melcangi’s only study on these matters. And as much as a disappointment it has been, we still have the genetic side of Baylor study supposedly coming out sometime in the future.

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