Human brain organelles study shows dopamine neurons must work a lot harder than those in primate relatives

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A team of neurologists, bioengineers and radiologists has found that two neurons in the human brain that code for dopamine production have to work harder than similar cells in primate relatives. The group has posted a paper describing their work on the bioRxiv preprint server.

Prior research has suggested that certain parts of the human anatomy suffer due to evolutionary changes—the knees and back, for example, are still adjusting to walking upright. In a similar vein, the teeth are still adjusting to constant changes in diet.

In this new study, the researchers wondered if the human brain, or parts of it, might still be adjusting to the massive increase in size that occurred over millions of years of evolution. To find out, the research team grew several brain organelles in their lab and compared them to brain parts from several primate relatives.

The team suspected such vulnerable brain points, if they exist, would likely involve the production of dopamine in the brain because the neurochemical plays such an important role in so many human activities, including learning, movement and processing emotions. The researchers started by using an imaging tool that allowed them to see that two regions in the brain rely on huge amounts of dopamine to function properly—the striatum and the prefrontal cortex, both of which are much larger in humans than in any other primate.

That led them to grow brain organelles with the two types of neurons that switch on and off as a way of communicating the need to code for dopamine production. They then genetically sequenced the neurons to learn more about what causes them to be switched on and off.

They discovered that such human neurons were turned on and off much more often when exposed to oxidative stress than all of the other primate relatives tested, possible evidence of an evolutionary stress point.

The researchers suggest the possibility that the brain must adjust in ways that stress certain parts, and because of that, it may have difficulty coping with certain brain ailments. Understanding such stress points, they further suggest, may lead to therapies specifically designed to treat disorders involving the dopaminergic system.

More information: Sara Nolbrant et al, Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability, bioRxiv (2024). DOI: 10.1101/2024.11.14.623592

Journal information: Evolutionary Biology , bioRxiv

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