Introducing the brain: dopamine, serotonin control genes (Introduction)

by David Turell , Tuesday, October 27, 2020, 21:35 (1276 days ago) @ David Turell

The latest findings from addiction reseaarch:

https://www.quantamagazine.org/the-epigenetic-secrets-behind-dopamine-drug-addiction-an...

"This is why cells in our body can be so different even though every cell has identical DNA. If the DNA is not unwound from its various spools — proteins called histones — the cell’s machinery can’t read the hidden code. So the genes that would make red blood corpuscles, for example, are shut off in cells that become neurons.

"How do cells know which genes to read? The histone spool that a specific gene’s DNA winds around is marked with a specific chemical tag, like a molecular Post-it note. That marker directs other proteins to “roll the tape” and unwind the relevant DNA from that histone (or not to roll it, depending on the tag).

"...[research] showed that serotonin has another function: It can act as one of those molecular Post-it notes. Specifically, it can bind to a type of histone known as H3, which controls the genes responsible for transforming human stem cells (the forerunner of all kinds of cells) into serotonin neurons. When serotonin binds to the histone, the DNA unwinds, turning on the genes that dictate the development of a stem cell into a serotonin neuron, while turning off other genes by keeping their DNA tightly wound.

"That finding inspired Maze’s team to wonder if dopamine might act in a similar way, regulating the genes involved in drug addiction and withdrawal. In the April Science paper that so surprised me, they showed that the same enzyme that attaches serotonin to H3 can also catalyze the attachment of dopamine to H3 — a process, I learned, called dopaminylation.

"Together, these results represent a huge change in our understanding of these chemicals. By binding to the H3 histone, serotonin and dopamine can regulate transcription of DNA into RNA and, as a consequence, the synthesis of specific proteins from them. That turns these well-known characters in neuroscience into double agents, acting obviously as neurotransmitters, but also as clandestine masters of epigenetics.

***

"In a commentary accompanying the research, Jean-Antoine Girault of Sorbonne University in Paris made a final, intriguing observation. We know that typical neural impulse firing works by causing a ripple effect of dynamic changes in calcium concentration inside neurons that eventually reach the nucleus. But Girault noted that the enzyme that catalyzes the attachment of dopamine to H3 is also regulated by levels of intracellular calcium. In this way, electrical chatter between neurons is relayed to the nucleus, suggesting that neural activity — driven by a behavior — could attach the dopamine epigenetic marker to genes responsible for drug-seeking behavior. That’s how the experiences one has in life can select which genes get read out, and which do not. Lamarck would be proud."

Comment: The functional aspects of gene expression controls in the brain are expanding with this research. The complexity increases and demands the recognition of design requirements. And of course, Lamarck is here to stay.