Page 7 of 9

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Fri May 31, 2019 4:05 pm
by AnhedonicApe
https://www.sciencedirect.com/science/a ... 9012004944 Maybe low dosing decitabine will be enough already, check out this:

''The cytidine analog 5-aza-2′-deoxycytidine (decitabine, DAC) has both a hypomethylating effect at low doses when incorporated into DNA and a cytotoxic effect at higher doses as a result of interfering with translation when incorporated into RNA. Thus, decitabine has been used at higher doses for its direct anti-leukemic effect, and is being tested at low doses for its ability to correct the malignant gene expression phenotype.''

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Sun Jun 09, 2019 3:58 pm
by AnhedonicApe
A different kind of chemo has been used for parkinson patients with succes. https://gumc.georgetown.edu/news-releas ... cal-trial/

“When used in higher doses for CML, nilotinib forces cancer cells into autophagy — a biological process that leads to the death of tumor cells. The dose used in CML treatment is significantly higher than what we used in our Parkinson’s study,” Moussa says. “It appears that in smaller doses once a day, nilotinib turns on autophagy for about four to eight hours — long enough to clean out the cells without causing cell death. Then proteins that build up again will be cleared when the drug is given again the next day.”

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Mon Jun 10, 2019 2:05 am
by Truskawa
I am also thinking of adding sodium butyrate.
Would that work similar to decitabine?

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Mon Jun 10, 2019 10:23 am
by AnhedonicApe
Truskawa wrote:I am also thinking of adding sodium butyrate.
Would that work similar to decitabine?


No, not even close, but i may benefit u

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Tue Jun 25, 2019 6:39 pm
by taarn
I'm very convinced our issues stem from epigenetic disruption. However our current options are very limited to revert back this altered gene regulation/expression.

"It incorporates into DNA strands upon replication, and then when DNA methyltransferases (DNMTs) such as DNMT1, are engaged to bind the DNA and to replicate the methylation to the daughter strand, DNMTs are bound to decitabine irreversibly and cannot disengage. Therefore, the action of decitabine is division-dependant, meaning the cells have to divide in order for the pharmaceutical to act."

^ This appliest to Decitabine and Azacitidine. These meds need cell division to prevent methylation. Most cells in the adult brain don't divide. However these can have effect throughout your body as well, I would say most likely help people with ED issues, for example.

HDAC inhibitors don't need cells to divide for altering gene expression, they may worth a shot. Vorinostat for example, or Valproate.

Any idea on demethylating agents that don't require cell division?

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Tue Jun 25, 2019 7:47 pm
by succubus76
taarn wrote:I'm very convinced our issues stem from epigenetic disruption. However our current options are very limited to revert back this altered gene regulation/expression.


Mmhhh Yea, is weird, Ive seen people react opposotely from benzos and alcoho after psych drugs. However, people that never touch ssris, never seems to have this problem. And is not a tolerance issue. Tolerance and react adversile are different things.

taarn wrote:"It incorporates into DNA strands upon replication, and then when DNA methyltransferases (DNMTs) such as DNMT1, are engaged to bind the DNA and to replicate the methylation to the daughter strand, DNMTs are bound to decitabine irreversibly and cannot disengage. Therefore, the action of decitabine is division-dependant, meaning the cells have to divide in order for the pharmaceutical to act."

^ This appliest to Decitabine and Azacitidine. These meds need cell division to prevent methylation. Most cells in the adult brain don't divide. However these can have effect throughout your body as well, I would say most likely help people with ED issues, for example.


Yeah, they could help a bit, but as you said, the root problem is directly in the Brain, because people report a less genital anestesia after dopaminergics (rasaline, Wellbutrin, meth, cocaine, etc) whitout pssd these meds helps for libido anyways, and since erogenous sensation is restored somewhat after dopaminergics, lets me to believe our problem in part is dopamine innhibition

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Tue Jun 25, 2019 8:17 pm
by Adweit saha
I came to know about genetic susceptibility of ssri..is there any risk factor thar it can be inherited to further generation from you

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Tue Jun 25, 2019 10:32 pm
by nasibi
Note: Post-mitotic cells means non-diving cells. And cell proliferation means cell division.

5-AzA, was applied in post-mitotic neurons (hippocampal neurons) and the dividing cells (Human SY5Y cell lines) in vitro. We found that 5-AzA treatment induced a time-dependent elevation in formaldehyde concentrations in the cultured medium of hippocampal neurons (Fig. 5F), and a dose-dependent elevation in formaldehyde levels in hippocampus by inhibiting DNMT activity in vivo (Fig. 5G, 5H).


Whether DNA demethylation occurs in post-mitotic neurons is rarely reported. Recently, however, Levenson and colleagues have found that 5-AzA (a DNA demethylation reagent) obviously induces DNA demethylation of reelin gene (increasing unmethylated DNA and decreasing methylated DNA) in hippocampal slice after adminitration 40 minutes, and this gene is expressed in hippocampal neurons35. In the present study, 5-AzA treatment elicited global DNA demethylation in hippocampal neurons in vitro and hippocampus of rats in vivo (Fig. 5E–5K). These data indicate that external stimuli can induce DNA demethylation and formaldehyde generation in post-mitotic neurons.
 

See Fig 5H how 5-Aza causes DNA demethylation in hippocampal (non-dividing) cells.

https://www.nature.com/articles/srep01807

In order to elucidate the regulatory mechanism of Brca1 in the retina, primary SD P3d rat retinal neurons were treated with 10 μm/mL Ara-C to inhibit cell proliferation on the second day and then were cultured for one week.


The DNA methyltransferase inhibitor 5-Aza-CdR is generally thought to act through incorporation into DNA during mitosis, thereby preventing methylation of the new DNA strand. However, 5-Aza-CdR also affects gene expression in post-mitotic, mature neurons [19]. Here, we found that Brca1 mRNA level was increased by 5-Aza-CdR, compared with controls... Thus, 5-Aza-CdR upregulates Brca1 expression in mature retinal neurons.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979323/

Here is another concise paper related to this topic:

Recent studies demonstrated that cytosine methylation in the genome can be reversed without DNA replication by enzymatic mechanisms based on base excision-repair pathways...


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335907/

Another one regarding DNA methylation in the brain:

While the use of DNMT inhibitors has indicated a wide range of potential roles for DNA methylation in neuronal plasticity and memory, it remains unknown how DNMT inhibition through administration of nucleoside analogs such as 5-azacytidine and zebularine result in demethylation in post-mitotic neurons. This effect is puzzling given that the inhibitory effect of the drugs is understood to depend on incorporation into genomic DNA during genome replication. One potential mode of action could be through inhibition of cyclical demethylation-methylation processes, for example by nucleoside analog incorporation into genomic DNA after Tet- and base excision repair-mediated demethylation of 5hmC, followed by inhibition of DNMT-mediated remethylation of the cytosine analog.


https://www.ncbi.nlm.nih.gov/pmc/articl ... 6/#s4title

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Tue Jun 25, 2019 11:23 pm
by AnhedonicApe

Re: New study reveals the epigenetic effects of Citalopram

Unread postPosted: Tue Jun 25, 2019 11:40 pm
by nasibi
AnhedonicApe wrote:I think this is a must read too: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864977/


I think it might be helpful if you could get Antonei Csoka also involved as he is the leading researcher in this whole PSSD and DNA methylation thing. The two studies I pm'd you about were both done by Csoka et al.