Do adult human brains renew their neurons?

TWO papers with starkly contradictory conclusions, published three weeks apart, have reignited debate about whether adult human brains can grow new neurons. For over a century, neuroscientists believed brains have acquired all the neurons they will ever have shortly after birth. But research over the past two decades has questioned this, producing evidence that new neurons are indeed generated in the adults of several species, people included. The matter is of more than just theoretical concern. Understanding how neurons are generated might lead to new ways of dealing with cognitive decline in ageing, neurodegenerative disease and even depression.

The conflicting studies both involved inspecting post-mortem brain samples using a technique called immunostaining. The first to press, by Arturo Alverez-Buylla and Shawn Sorrells of the University of California, San Francisco, was published on March 15th in Nature. It claims that neurogenesis happens rarely, if at all, in adults. The other, by Maura Boldrini and René Hen at Columbia University, was published on April 5th in Cell Stem Cell. It claims neurogenesis persists through adulthood at a largely unchanged rate.

Immunostaining uses antibodies that bind to particular proteins and fluoresce in particular colours. Employing it, both teams focused their attention on DCX and PSA-NCAM, two proteins found more abundantly in newly generated nerve cells than in older ones. They looked, in particular, at the hippocampuses, two parts of the brain (see picture) involved in memory formation—a process that might easily be assisted by the generation of new neurons.

Using DCX and PSA-NCAM as indicators of youthful nerve cells, Dr Alverez-Buylla and Dr Sorrells describe a picture of abundant neurogenesis in prenatal and infant brains, which then declines sharply in the first year of life. The oldest hippocampus in which they saw new neurons had come from a 13-year-old. This supports the historical belief that adult brains do not generate new neurons. Dr Boldrini and Dr Hen, in contrast, saw signs of youthful neurons in people up to the age of 79.

How such contradictory conclusions emerged from similar approaches is now being debated. One difference was that Dr Alverez-Buylla and Dr Sorrells used samples collected up to 48 hours after death, whereas the upper limit used by Dr Boldrini and Dr Hen was 26 hours. That might be important. Studies on rats suggest DCX can break down within hours of death.

Moreover, though both teams used immunostaining, their procedures differed in other respects. In particular, Dr Boldrini and Dr Hen looked only at teenagers and adults, so could not have picked up the change that Dr Alverez-Buylla and Dr Sorrells saw in the earliest years, which provided an important reference point for the effectiveness of immunostaining. Conversely, Dr Boldrini and Dr Hen used other lines of evidence, such as the volume of the hippocampus (which did not seem smaller in old brains than in young ones), to support their conclusions.

The upshot is that old scientific cliché: “more research is needed”. But the coincident publication of these two papers, each plausible in itself, is a useful reminder of the requirement, in science, to check the work. Then check it. Then check it again.

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