Developmental Biology - Brain|
Can Adult Brains Create New Neurons?
Lessons learned from the adult neurogenesis debate...
Starting in the 1960s, a question of whether adult humans can generate new neurons has swayed back and forth from "yes, in some places in the brain" to "no, not at all." This debate reignited in 2018 with two headline-grabbing papers in Cell Stem Cell and Nature, published only weeks apart, made convincing arguments for each side.
In a review paper published January 24 in the journal Trends in Neurosciences, University of British Columbia professor Jason Snyder PhD, Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Canada, argues that these conflicting reports are reconcilable. He believes issues related to the way we study the brain draws attention away from how enhancing adult neurogenesis, even artificially, could benefit human health.
"It's clear that there is a lot of controversy, which to me seems unwarranted because a yes or no for 'is there adult neurogenesis' is a little too simplistic and distracts us from other important questions," says Snyder. "It's worth asking if methodological differences are the only reason that some people aren't finding new neurons or if there is some truth to the observations that neurogenesis may be limited with age in humans. I wanted to take a quantitative look at the research and see where it all leads."
Snyder has identified that labs finding more neurogenesis in mice than in humans conduct their studies in young mice. Human research is often conducted in adults from middle to old age. Primates and rodents develop most neurons at different times.
• Human peak neurogenesis is in early pregnancy.
• Mouse neurogenesis continues after birth.
Mouse neurogenesis studies might be reflecting the natural consequences of rodent brain development happening later in their lives.
"The literature also indicates that if you look at a middle-aged rodent, it doesn't have much neurogenesis either," he says. "If we were to study the same in relative-aged human subjects, I don't think the story is much different. For much of the adult lifespan, we're not bursting at the seams with new neurons. While that may be disconcerting for people, it does reconcile the field: it's not that some studies are right and some are wrong."
Though still uncertain whether neurogenesis in adult humans occurs, Snyder says the evidence suggests it is happening at low rates in specific parts of the brain. Most likely in the hippocampus, where new memories form.
There are many questions unanswered regarding what these new neurons would do, whether they have different functions throughout the lifecycle, and whether they would have therapeutic relevance.
Snyder: "The neurogenesis field is a great case study because it may be one of the most dramatic examples of progress ping-ponging back and forth over the course of 50 years. This is just how science works. But, we shouldn't let our search for a smoking gun stop us from asking better questions."
• Animal work has revealed that immature neurons born in the adult dentate gyrus have key cellular and behavioral functions.
• Recent reports are conflicted about whether adult neurogenesis occurs in humans.
Discrepancies could arise from species differences in neuro-developmental timing and differences in subject ages.
• Regardless of its extent, postnatally, an extended period of neurogenesis may produce a heterogeneous population of dentate gyrus neurons, due to prolonged cellular maturation and differences in the stage of the lifespan when neurons are born.
• These developments warrant a recalibration of when and how dentate gyrus neurogenesis contributes to cognition and mental health in humans.
Conflicting reports about whether adult hippocampal neurogenesis occurs in humans raise questions about its significance for human health and the relevance of animal models. Drawing upon published data, I review species’ neurogenesis rates across the lifespan and propose that accelerated neuro-developmental timing is consistent with lower rates of neurogenesis in adult primates and humans. Nonetheless, protracted neurogenesis may produce populations of neurons that retain plastic properties for long intervals, and have distinct functions depending on when in the lifespan they were born. With some conceptual recalibration we may therefore be able to reconcile seemingly disparate findings and continue to ask how adult neurogenesis, as studied in animals, is relevant for human health.
Jason S. Snyder.
Work in the Snyder lab is supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Michael Smith Foundation for Health Research.
Trends in Neurosciences, Snyder, J.: "Recalibrating the relevance of adult neurogenesis" https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(18)30314-X
Trends in Neurosciences (@TrendsNeuro), published by Cell Press, is a monthly review journal that brings together research covering all disciplines of the neurosciences, allowing researchers, students and teachers to keep up with the last developments, insights, and future directions in the field Visit: http://www.cell.com/trends/neurosciences. To receive Cell Press media alerts, please contact email@example.com.
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Image: Neurons in the infant brain. Image source: snyderlab.com