The Myth of Human Adult Neurogenesis?

By Neuroskeptic | July 27, 2016 8:49 am

In a new paper that could prove explosive, Australian neuropathologists C. V. Dennis and colleagues report that they found very little evidence for adult neurogenesis in humans.

In recent years, the idea that neurogenesis – the production of new neurons – occurs in specific regions of the adult brain has become widely accepted, and much discussed. Disruptions to neurogenesis have been proposed to play a role in stress, depression, and other disorders.

However, Dennis et al. say that neurogenesis in adults occurs at such a low level as to be “functionally insignificant”. They examined 23 preserved human brains taken from individuals who had died at ages ranging from 0.2 years up to 59 years. The authors focussed on two regions, the subventricular zone (SVZ), and the subgranular zone (SGZ) of the hippocampus; these are the two main areas where adult neurogenesis has been reported.

To test for markers of ongoing neurogenesis, Dennis et al. used antibodies to selectively mark three proteins: Ki67, PCNA, and doublecortin. The first two are markers of proliferating cells, while the third is specific to immature neurons.

The results showed that, in the SVZ, Ki67+ and PCNA+ cells were present at all ages, showing that some kind of cells were proliferating (albeit the number of proliferating cells declined with age). However, crucially, doublecortin+ cells were only present in children; they were not found in any individuals over the age of 16, suggesting that the generation of new neurons had ceased.dennis_dcxThe situation was similar in the SGZ: Ki67+ and doublecortin+ cells were very common in children but were usually absent in adults (found in only 3 out of 8 adult brains). The authors conclude that

A combination of Ki67 and doublecortin immunoreactivity demonstrates that in humans, the density of proliferating cells, and neuroblasts in particular, declines markedly with age in the SVZ and SGZ and by four years of age is no greater than in the adjacent parenchyma… this low level of neurogenesis in neurologically normal adult humans suggests that any further reduction is unlikely to significantly contribute to the pathogenesis of neurodegenerative diseases.
What about the famous 2013 study by Kirsty L Spalding and colleagues which did report evidence for adult human hippocampal neurogenesis, using a different method? Dennis et al. say that the two sets of results are actually compatible. Spalding et al. estimated a rate of neurogenesis of 700 new neurons per day in adults. This rate, Dennis et al. say, is consistent with the low levels of doublecortin+ cells they counted in the SGZ (in the 3/8 adults who had any).

So it’s fair to say that Dennis et al. don’t quite rule out all neurogenesis in adults. However, the authors say that if human adult neurogenesis takes place, it does so at an extremely low rate: relatively speaking, it’s about 10 times lower than the rate seen in adult rodents.

The marked differences between infants and adults in the current study suggests that in humans, the decline in neurogenesis with age is more rapid than in other mammals and that in adults, neurogenesis is functionally insignificant.

ResearchBlogging.orgDennis CV, Suh LS, Rodriguez ML, Kril JJ, & Sutherland GT (2016). Human adult neurogenesis across the ages: An immunohistochemical study. Neuropathology and applied neurobiology PMID: 27424496

CATEGORIZED UNDER: neurogenesis, papers, select, Top Posts
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  • Gabriel Castellanos

    Post-mortem studies show that neurogenesis in “non-healthy adults” occurs at a low level? Isn´t the same in “non-healthy” small animals?

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      True. This raises the question of how healthy the individuals in Dennis et al.’s study were. They are all described as being ” neurologically normal”. The causes of death are various: drowning (5), cardiac (6), respiratory (6) and a few others. There are no details on the subjects’ state of health before they died.

      • paul

        Lots of people have lived stable, relatively-easy lives in the past decades. If that’s the case, then people often would, could, and should not have much neurogenesis after childhood developmental periods. BUT, that doesn’t mean that we lose that capacity.

  • obadiah_edomite

    well-preserved brains of scientists will remain unchanged for at least 100 years.

  • https://twitter.com/committovote LincolnX

    I can attest that no new neurons are being born in my brain.

    • paul

      Sorry to hear that! 😉

  • Jenny H

    I though that it was the formation of new/stronger synapses rather than neurons that was important?

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Formation of synapses certainly is important (and that happens everywhere in the brain) but many people believe that new neurons (especially in the SGZ of the hippocampus) are important too. This new study calls that into question.

    • paul

      Both/either can be important, depending on the circumstances.

  • smedgehammer

    So, is this basically saying that the brain is done growing by age 16?

    • paul

      No. It can be fairly set if you let it. Developmental periods certainly allow for more neurogenesis and circuit formation. BUT, you can continue to be neuroplastic throughout life if you engage the mechanisms that spur neurogenesis.

  • paul

    There are several things KNOWN scientifically to spur neurogenesis. Those include: thirst, hunger, intense exercise, and marijuana.

  • http://lenr-coldfusion.com/ Jack Cole

    While this is an interesting study, I wonder what would be made of studies showing increases in brain volume in response to certain interventions (e.g., aerobic exercise in older adults (1)).

    The conclusion that “neurogenesis is functionally insignificant” would not seem to be warranted at this point based on at least 2 factors.

    a). small sample size
    b). does not indicate if significant neurogenesis can be induced by an intervention (medication, rehab activity, etc…)

    Perhaps it would have made more sense to conclude, “The methods used in this study failed to demonstrate functionally significant levels of neurogenesis in the adult samples.”

    (1). http://biomedgerontology.oxfordjournals.org/content/61/11/1166.short

    • asciibrain

      Does the methods used in this study offer real information about impact on functionality, or are the conclusions based on an intuitive judgement about the small number of new neurons per day?

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  • Deirdre Oliver

    There goes the last few years of claims that ElectroconvulsiveTherapy helps depression by creating new neurones. Actually I thought they were glial cells anyway. And what happens to these brave new cells when the effects of ECT wear off after a few weeks as they invariably do? Or are these studies just more of the spurious pseudoscience for which psychiatry is renowned?

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Well it’s possible in theory that ECT does trigger neurogenesis, even if neurogenesis is normally absent in adults. Maybe ECT re-activates it? I don’t know.

    • stmccrea

      I suspect that any glimmer of a positive result in this area was grasped onto violently by supporters of ECT, because there is next to no understanding of why ECT “works” or what “works” even really means. My experience is that the world of mental health is very political, and confirmation bias abounds, at least where there is money to be made.

      • Deirdre Oliver

        That the `studies’ can be easily taken apart by an interested lay person with only a rudimentary scientific education speaks strongly in favour of confirmation bias with elements of the true believer syndrome. Actually they are well aware of how it works. It works, as it was designed to do, by shutting the brain down – Moniz 1938)”… “destroy the more or less fixed arrangements of cellular connections that exist in the brain…removing their fixed pathological brain circuits.” 1942, Myerson; “The reduction of intelligence is an important factor in the curative process…” 1946 – Wilcox, “…shock therapies…must necessarily depend upon brain tissue destruction.” 1989 – Fink,, “The basis of improvement is similar to that of craniocerebral trauma (head injury).” All they do is attribute `improvement’ to the symptoms of Brain trauma.
        Interestingly the studies that discuss neurogenesis (2012-16) find, among other things, increased `volume’ in the amygdala & hippocampus but decreased `grey matter’ in the frontal lobes??? What they appear to do is document significant damage and then attempt to claim that this is a good thing, probably because since the damage is gross enough to be seen on MRI scans, they have to. The difficulties arise because there is no evidence that depression is caused by any kind of `lack’ of `volume’ in some areas, or a surfeit in others. Mind you these studies are very small and there is a distinct air of pseudoscience in the use of jargon, leaping to conclusions, backward reasoning, subjective validation, unproven core principles etc.
        I was under the impression that neurogenesis when it did occur was usually the consequence of trauma and that most new cells died within a short time? If that’s the case it’s further proof that ECT is Trauma.

        • stmccrea

          You said it all.

    • Troy

      Very disappointed anti-psychiatry loons have such a strong presence on this blog. ECT has likely saved millions of people at this point, and while grey matter volume increases, unlikely through neurogenesis by itself (angiogenesis, synaptogenesis, gliogenesis), may not be the prime or only way it works, there’s growing evidence for it, and no evidence in recent years for “tissue destruction”, as Fink (almost alone now) asserts based on old studies.

      “That the `studies’ can be easily taken apart by an interested lay person with only a rudimentary scientific education speaks strongly in favour of confirmation bias with elements of the true believer syndrome. ”

      You indeed say it all. Dunning-Kruger effect.

      Let’s not throw the whole field into disrepute over one paper. They examined the brains of relatively healthy adults not currently being treated with anything. I don’t see how it challenges the idea that antidepressants may restore neurogenesis above and beyond the normal levels, as that was not tested for, let alone the effects of ECT on the hippocampus and other brain regions. More briefly, anyone honest might find these papers interesting:

      http://www.ncbi.nlm.nih.gov/pubmed/20190603

      http://www.ncbi.nlm.nih.gov/pubmed/27271858

  • Deirdre Oliver

    Of course one might have to establish whether it is a lack of new cells that causes depression in the first place, and/or whether neurogenesis by electrical means is a response to the trauma of the passage of 450 volts and 140 square wave pulses per second for 8 seconds through neural tissue. Do we know whether other electrical injuries generate neurogenesis?

  • RobertLaity

    That Neuroplasticity exists in Humans is known science.

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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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