[smart (OP)]

How exactly does prolonged psychotropic drugs administration may induce dopamine-related transcription factors deficit in the prefrontal cortex?

What do you think?

[evan_au]

It is a mechanism called “homeostasis “ by biologists, and “negative feedback “ by engineers.
- your body tries to maintain itself in the optimum settings, despite external influences
- if you try to disturb your body’s equilibrium by taking chemicals (especially chemicals which mimic biological molecules), your body attempts to compensate by down regulating production of the natural chemical, and/or reducing the sensitivity of the receptor. This leads to chemical dependence.
- a common example is opioid dependence

This regulation can use a number of mechanisms
- some of them are epigenetic
- including small RNAs which regulate transcription of other genes - to increase or decrease it
- and DNA methylation which can also reduce gene transcription
- the DNA must be transcribed into RNA before it can be transcribed into proteins like dopamine, endorphins (natural opioids) or endocannabinoids (natural cannabis molecules).

Mess with your biochemistry only after careful study (preferably double-blinded)!

[smart (OP)]

Thanks @evan_au

[smart (OP)]

Is there positive and negative dopamine transcription factors?

Assuming psychotropic drugs negatively affect dopamine transcription, is it possible to reverse dopamine neurotransmission through selective activation of the Nurr1 pathway?

[evan_au]

prolonged psychotropic drugs administration may induce dopamine-related ... deficit?

It turns out that methamphetamine (commonly known as "meth") can cause the death of brain cells that normally produce dopamine and serotonin, two essential brain signaling molecules.

Effectively, self-administered Parkinson's disease...
See: https://en.wikipedia.org/wiki/Methamphetamine#Overdose

Is there positive and negative dopamine transcription factors?

Less than 2% of human DNA is used to produce proteins, and this was the focus of the Human Genome Project. Until recently, the 98% "non-protein coding" regions of the DNA were commonly called "Junk DNA", as if they did nothing. This condescending term shows how little we know about them.

We are now discovering more about these regions by analysing the RNA in a cell, rather than the DNA. Something like 80% of DNA is transcribed into RNA in the cell. Now the ENCODE project is trying to find out what the other 78% is doing.

In fact, many gene regulation mechanisms are poorly understood. Whether a gene can be downregulated and/or upregulated depends on the historical genetic needs of the species.

If a gene can be down-regulated, then it may be possible to up-regulate it by down-regulating the down-regulator segment of DNA? (I hope that isn't a circular argument...)

I understand that the human problem with cholesterol and heart disease is due to the fact that this chemical is so essential for life that we can produce all we need. If there is little cholesterol in the diet (in vegans, for example), production can be upregulated. However, if there is an excess in the diet (eg the modern "Western" diet),  the body can downregulate to near-zero, but can't go into "negative" production - so cholesterol sometimes accumulates in artery walls, a marker of heart disease.
See: https://en.wikipedia.org/wiki/Noncoding_DNA

Assuming psychotropic drugs negatively affect dopamine transcription, is it possible to restore dopamine neurotransmission through selective activation of the Nurr1 pathway?

I don't know.

But if you keep killing brain cells, the Nurr1 pathway won't restore them.

[smart (OP)]

Is a RNA-guided dopamine transcription factor (Nurr1) reversible?

[evan_au]

Is a RNA-guided dopamine transcription factor (Nurr1) reversible?

The great reverser is fertilisation of an egg by a sperm. This erases almost all* epigenetic markers and transcription factors so the new zygote can start off from a known "blank slate".

But I assume you are talking about a human adult.

You might be able to resume expression of a gene in an adult if:
- you find the bit of DNA that produces the stretch of micro-RNA which controls the gene expression
- You then locate the promoter segment of DNA that encourages production of this particular micro-RNA
- You then identify what turns on this promoter
- And then disable that
- Which might involve getting some new factor past the blood-brain barrier and into the cells of interest

However, these networks of micro-RNAs and promoters (and gene regulation in general) is poorly understood at present.

So I am afraid this is beyond our current technology.

* There are a few residual "imprinted" genes.
See: https://en.wikipedia.org/wiki/Genomic_imprinting