Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress

I found a really interesting review article in the Hindawi Open Access Journal Database. The file was too large to upload as a study and my subsequent attempts at screenshotting the pages and inserting into a word document to be converted into a PDF were unsuccessful for upload. So I thought I'd self-compose a little article that draws on the abstract from the pertaining review, as well as explore Epigenetics for those unfamiliar with this biological field of study.

Epigenetics refers to the study of heritable changes in our genome (the complete set of all our genes) that occur without altering the DNA or genetic code.
All living beings are made up of cells (humans have about 37 trillion cells). In the nucleus of each cell, you’ll find our DNA. The sequence of DNA bases (A,C,T and G) defines our genes or genetic code.
Humans have over 20,000 genes on long strands of DNA, which is tightly packaged around structures called histones. Together, the histones and DNA are referred to as the chromatin.
In the nucleus the genetic code is ‘read’ and transcribed into messages (RNA), which is translated into proteins. These proteins then carry out the functions in each cell of the body.
Of course not all genes/proteins are required by all cells all the time – they are turned on (or expressed) and off somehow – this is where Epigenetics comes in.
‘Epi’ means on top of or above – so Epigenetics refers to mechanisms that affect genes from above, i.e, not affecting the genetic code itself. We know of two main epigenetic mechanisms controlling gene expression:

1. DNA methylation, which chemically modifies the base C, altering how the genetic code is read;

2. Chromatin remodelling, which alters the availability of genes for reading.

Disrupted gene expression underlies many human diseases such as cancer; the study of both genetics and epigenetics is helping our race to further understand such diseases and help to develop preventative measures as well as novel medical treatments.
Gene expression can be disrupted or influenced by both intrinsic and extrinsic factors (i.e factors from inside and outside of the body).
Chemical and physical environmental stressors, diet, lifestyle habits, and pharmacological treatments can affect the epigenome during lifetime and carry the potential to impact epigenetic changes on pathophysiological processes.

Methamphetamine is a widely abused drug, which possesses neurotoxic activity and powerful addictive effects.
Understanding methamphetamine toxicity is key beyond the field of drug abuse since it allows getting an insight into the molecular mechanisms which operate in a variety of neuropsychiatric disorders. In fact, key alterations produced by methamphetamine involve dopamine neurotransmission in a way, which is reminiscent of spontaneous neurodegeneration and psychiatric schizophrenia. Thus, understanding the molecular mechanisms operated by methamphetamine represents a wide window to understand both the addicted brain and a variety of neuropsychiatric disorders. This overlapping, which is already present when looking at the molecular and cellular events promoted immediately after methamphetamine intake, becomes impressive when plastic changes induced in the brain of methamphetamine-addicted patients are considered. Thus, the linked manuscript is an attempt to encompass all the molecular events starting at the presynaptic dopamine terminals to reach the nucleus of postsynaptic neurons to explain how specific neurotransmitters and signalling cascades produce persistent genetic modifications, which shift neuronal phenotype and induce behavioural alterations.
In the linked review paper, special emphasis is posed on disclosing those early and delayed molecular events, which translate an altered neurotransmitter function into epigenetic events, which are derived from the translation of postsynaptic noncanonical signalling into altered gene regulation. All epigenetic effects are considered in light of their persistent changes induced in the postsynaptic neurons including sensitization and desensitization, priming, and shift of neuronal phenotype.

For more information please visit... https://doi.org/10.1155/2018/4982453