When does the brain grow? Research shows that the brains of mice and primates mature at the same rate

An Argonne study found that short-lived mice and longer-lived primates develop brain synapses at exactly the same time, challenging assumptions about disease and aging. What does this mean for humans – and for yesterday’s research?

Mice typically live two years and monkeys 25 years, but the brains of both appear to develop synapses at the same time. This discovery, the result of a recent study led by neuroscientist Bobby Kasthuri of the U.S. Department of Energy’s (DOE) Argonne National Laboratory and colleagues at the University of Chicago, comes as a shock to neuroscientists. The article is published in the journal Natural communications.

Until now, brain development was thought to occur more rapidly in mice than in other longer-lived mammals, such as primates and humans. Those who studied the brain of a 2-month-old mouse, for example, assumed that the brain had already finished developing because its overall lifespan was shorter. In contrast, the brain of a 2-month-old primate was still considered to be undergoing developmental changes. As a result, the brain of a two-month-old mouse was not considered a good model for comparison with that of a two-month-old primate.

This hypothesis appears completely wrong, and the authors believe it will call into question many findings using data from the brains of young mice as a basis for research into various human conditions, including autism and other neurodevelopmental disorders.

“A fundamental question in neuroscience, particularly in the mammalian brain, is how do brains grow? » said Kasthuri. “It turns out that mammalian brains mature at the same rate, at every absolute stage. We’re going to have to rethink aging and development now that we see it’s the same clock.”

Gregg Wildenberg is a researcher at the University of Chicago and lead author of the study with Kasthuri and graduate students Hanyu Li, Vandana Sampathkumar and Anastasia Sorokina. He closely observed the neurons and synapses activated in the brains of very young mice. He marveled that the baby mouse crawled, ate, and behaved as expected, even though it had virtually no measurable connections in its brain circuits.

“I think I found a synapse on an entire neuron, and it’s shocking,” Wildenberg said. “This living baby animal existed outside the womb six days after birth, behaving and experiencing the world without any neurons in its brain actually connected to each other. We must be careful not to overinterpret our results, but it’s fascinating.”

Neurons in the brain are different from neurons in cells of all other organs because brain cells are post-mitotic, meaning they never divide. All other cells in the body – liver, stomach, heart, skin, etc. – divide, are replaced and deteriorate over the course of life. This process begins during development and ultimately ends with aging. However, the brain is the only mammalian organ that has essentially the same cells on the first and last day of life.

To complicate matters, the first embryonic cells of each species appear identical. If fish, mouse, primate and human embryos were all put together in a petri dish, it would be virtually impossible to determine which embryo would develop into which species. At a mysterious moment, a change in developmental programming occurs within an embryo and a single specific species emerges. Scientists would like to understand the role of brain cells in brain development as well as physical development within species.

Kasthuri and his team were able to advance their recent discovery through the Argonne Leadership Computing Facility (ALCF), a DOE Office of Science user facility. The ALCF is capable of processing huge data sets – “terabytes, terabytes and more terabytes of data,” Kasthuri said – to examine brain cells at the nanoscale. The researchers used the supercomputer to examine every neuron and count every synapse in multiple brain samples at multiple ages from both species. Collecting and analyzing this level of data would have been impossible, Kasthuri said, without the ALCF.

Kasthuri knows many scientists will want more data to confirm the recent study’s findings. He himself reconsiders the results of past research in the context of new information.

“One of our previous studies compared the brain of an adult mouse to that of an adult primate. We thought that primates are more intelligent than mice, so each neuron should have more connections, be more flexible, have more roads, etc.,” he explained. “We found that exactly the opposite is true. Primate neurons have far fewer connections than mouse neurons. Now, looking back, we thought we were comparing similar species, but that wasn’t the case. case. We compared a 3 month old mouse to a 5 year old mouse. 1 year old primate.”

The implications of the research for humans are unclear. On the one hand, behaviorally, humans develop more slowly than other species. For example, many four-legged mammals can walk within the first hour of their lives, whereas humans often take more than a year before taking their first steps. Are the rules and rhythm of synaptic development different in the human brain compared to other mammalian brains?

“We think something remarkable, something magical, will be revealed when we are able to look at human tissue,” said Kasthuri, who suspects humans might have a completely different timeline. “That’s where the clock that’s the same for all these other mammal species can be broken.”

Wildenberg hopes that the information gathered during the study will lead to the development of pharmaceutical products that better target human neurological disorders and diseases.

“Mouse models could be ideal for developing cardiovascular drugs because hearts, which are essentially pumps, work the same way across species,” he said. “However, developing drugs for neurological diseases is extremely difficult. It is important to understand how the brains of different species evolve so that scientists can adapt their approaches based on the brain’s innovations and adaptations.”