Introducing the brain: human neurons grow very slowly (Introduction)

by David Turell , Tuesday, May 30, 2023, 14:53 (541 days ago) @ David Turell

Compared to mice:

https://www.the-scientist.com/news-opinion/mitochondrial-metabolism-dictates-neurons-gr...

"Human brains grow extraordinarily slowly—a trait many neuroscientists speculate is related to our distinctive intellect. But how and why a human neuron takes years to grow when a mouse neuron grows for mere weeks has remained unclear. Now, scientists have uncovered one piece of the puzzle: Neuron growth is mediated by its mitochondria’s metabolism, according to a January 26 study in Science. The finding could not only help answer fundamental questions about brain development, the study authors say it could widen treatment options for developmental disorders.

“'This is the most exciting study I’ve read in a while,” says Suzana Herculano-Houzel, a biologist and neuroscientist at Vanderbilt University who wasn’t involved in the research. “It opens a path for finding answers to, what is to me, one of the biggest questions we have: What makes different brains different?”

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"...he and his colleagues at the time noted that every single aspect of the neuron, from its dendrites to its synapses to its axon, grows in synchrony, indicating that the growth is regulated by a ubiquitous, basal component of the cell. Other research had posited that mitochondria may somehow play important roles in the development of cells. So he and his team set out to investigate whether mitochondria are involved in regulating neuron growth.

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"Vanderhaeghen explains, as neurons don’t develop at the same rate as one another, even when their original stem cells are created at the same time. However, stem cells can only become neurons after promoter NeuroD1 is activated. So Vanderhaeghen and colleagues came up with a genetic tool that uses an engineered recombinase enzyme called CreER that identifies when NeuroD1 is turned on and immediately tags the neuron—essentially flagging its “birth.” With the ability to date the neurons, Vanderhaeghen and his team could start testing the effect mitochondria have on neuron growth rates.

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"The team knew they could manipulate mitochondrial respiration pharmacologically, so they sped up metabolism in human cortical neurons in vitro. Vanderhaeghen recalls a moment in the lab looking at the neurons; at only a few weeks old, the accelerated cortical neurons were considerably more mature than a normal human neuron. “To us, this was a big eureka moment,” he says. “There we thought, ‘this is it.’”

"The scientists tested the same principle in vivo, speeding up the mitochondrial metabolism of human neurons and implanting them into mice, as well as slowing down the mitochondrial metabolism of mouse neurons both in culture and inside the mice’s brains. The results from both in and out of the brain aligned: Human neurons with increased metabolic rates grew faster than normal, and mouse neurons with decreased mitochondrial metabolic rates displayed slower growth.

"Many scientists theorize that the human brain’s slow growth is part of what allows for our unique mental capacities. Knowing that a metabolism regulator can slow or speed up that growth will allow for further studies into what makes us human, Vanderhaeghen posits."

Comment: it would be interesting to study ape neuron mitochondrial metabolism, brains closer to us in evolution. But it does help explain why full-grown adolescents don't have a fully developed frontal lobes until age 25.