Saturday, October 31, 2020

"The Epigenetic Secrets Behind Dopamine, Drug Addiction and Depression"

So, it's a little more complex than neurotransmitter cascades and our old pals the D3 and D4 receptors.

From Quanta Magazine, October 27:

New research links serotonin and dopamine not just to addiction and depression, but to the ability to control genes.

As I opened my copy of Science at home one night, an unfamiliar word in the title of a new study caught my eye: dopaminylation. The term refers to the brain chemical dopamine’s ability, in addition to transmitting signals across synapses, to enter a cell’s nucleus and control specific genes. As I read the paper, I realized that it completely upends our understanding of genetics and drug addiction. The intense craving for addictive drugs like alcohol and cocaine may be caused by dopamine controlling genes that alter the brain circuitry underlying addiction. Intriguingly, the results also suggest an answer to why drugs that treat major depression must typically be taken for weeks before they’re effective. I was shocked by the dramatic discovery, but to really understand it, I first had to unlearn some things.

“Half of what you learned in college is wrong,” my biology professor, David Lange, once said. “Problem is, we don’t know which half.” How right he was. I was taught to scoff at Jean-Baptiste Lamarck and his theory that traits acquired through life experience could be passed on to the next generation. The silly traditional example is the mama giraffe stretching her neck to reach food high in trees, resulting in baby giraffes with extra-long necks. Then biologists discovered we really can inherit traits our parents acquired in life, without any change to the DNA sequence of our genes. It’s all thanks to a process called epigenetics — a form of gene expression that can be inherited but isn’t actually part of the genetic code. This is where it turns out that brain chemicals like dopamine play a role.

All genetic information is encoded in the DNA sequence of our genes, and traits are passed on in the random swapping of genes between egg and sperm that sparks a new life. Genetic information and instructions are coded in a sequence of four different molecules (nucleotides abbreviated A, T, G and C) on the long double-helix strand of DNA. The linear code is quite lengthy (about 6 feet long per human cell), so it’s stored neatly wound around protein bobbins, similar to how magnetic tape is wound around spools in cassette tapes.

Inherited genes are activated or inactivated to build a unique individual from a fertilized egg, but cells also constantly turn specific genes on and off throughout life to make the proteins cells need to function. When a gene is activated, special proteins latch onto DNA, read the sequence of letters there and make a disposable copy of that sequence in the form of messenger RNA. The messenger RNA then shuttles the genetic instructions to the cell’s ribosomes, which decipher the code and make the protein specified by the gene.

But none of that works without access to the DNA. By analogy, if the magnetic tape remains tightly wound, you can’t read the information on the cassette. Epigenetics works by unspooling the tape, or not, to control which genetic instructions are carried out. In epigenetic inheritance, the DNA code is not altered, but access to it is....


I'm still trying to get my head around what's real and what's hype in epigenetics. In the introductory riff from "Labor Markets: 'Rural America Needs Triage'" I sound more certain than I actually am.

Some concepts, profound in their simplicity, that policymakers will have to internalize before the human toll of current economics—whether fast suicides by firearms or hanging or slow suicides by opioids, self-medicating with carbohydrates and booze leading to epidemic levels of obesity, cirrhosis and diabetes, from first generation poverty leading to  multi-generational epigenetic DNA methylation of genes linked to depression—the policy wonks have to get the basics down first....

See also:

"Do Your Grandmother’s Experiences Really Make It Into Your Genes?"

"It’s now possible to map a person’s lifetime exposure to nutrition, bacteria, viruses, and environmental toxins—which profoundly influence human health"