The results here will cause some upheaval in the research community if verified, and will do doubt lead to considerable debate regardless of the outcome. For decades it is has been considered that neurogenesis, the production and integration of new neurons in the brain, continues past childhood, albeit at a lower rate. This is based largely on studies in mice, but also on a range of human evidence. The researchers here suggest that this is wrong, and in fact humans are not like mice in this regard: we do not generate new neurons at any detectable level as adults. This question of adult neurogenesis has great influence on the strategies adopted in the development of therapies that might enhance maintenance of the brain. This is a topic of considerable importance to the future of human rejuvenation: we are our brains, and damage and loss must be repaired in situ. If there are no naturally occurring mechanisms to achieve that goal in some or all of the brain, this suggests that the task will be that much harder to safely achieve.
One of the liveliest debates in neuroscience over the past half century surrounds whether the human brain renews itself by producing new neurons throughout life, and whether it may be possible to rejuvenate the brain by boosting its innate regenerative capacity. Now scientists have shown that in the human hippocampus - a region essential for learning and memory and one of the key places where researchers have been seeking evidence that new neurons continue to be born throughout the lifespan - neurogenesis declines throughout childhood and is undetectable in adults.
The findings present a challenge to a large body of research which has proposed that boosting the birth of new neurons could help to treat brain diseases such as Alzheimer's disease and depression. But the authors said it also opens the door to exciting new questions about how the human brain learns and adapts without a supply of new neurons, as in seen in mice and other animals. It was once neuroscientific dogma that the brain stops producing new neurons before birth. In the 1960s, experiments in rodents first suggested that new neurons could be born in the adult mammalian brain, but these results remained highly controversial until the 1980s, it was shown that new neurons are born and put to use throughout life in several parts of the songbird brain.
These findings launched a whole field of research. Much work has focused on a region of the hippocampus called the dentate gyrus (DG), where rodents produce newborn neurons throughout life that are thought to help them form distinct new memories, among other cognitive functions. Rodent studies have shown that DG neurogenesis declines with age, but is otherwise quite malleable - increasing with exercise, but decreasing with stress, for example - leading to popular claims that we can boost brain regeneration by living a healthy lifestyle. Beginning in the late '90s, a handful of studies reported evidence of adult neurogenesis in the human brain, either by estimating the birth dates of cells present in postmortem brain specimens or by labeling telltale molecular markers of newborn neurons or dividing neural stem cells. However, these findings, some of which were based on small numbers of brain samples, have remained controversial.
In the new study, researchers collected and analyzed samples of the human hippocampus. They analyzed changes in the number of newborn neurons and neural stem cells present in these samples, from before birth to adulthood, using a variety of antibodies to identify cells of different types and states of maturity, including neural stem cells and progenitors, newborn and mature neurons, and non-neuronal glial cells. The researchers also examined the cells they labeled based on their shape and structure - including imaging with high-resolution electron microscopy for a subset of tissue samples - in order to confirm their identity as neurons, neuronal stem cells, or glial cells.
The researchers found plentiful evidence of neurogenesis in the dentate gyrus during prenatal brain development and in newborns, observing an average of 1,618 young neurons per square millimeter of brain tissue at the time of birth. But the number of newborn cells sharply declined in samples obtained during early infancy: dentate gyrus samples from year-old infants contained fivefold fewer new neurons than was seen in samples from newborn infants. The decline continued into childhood, with the number of new neurons declining by 23-fold between one and seven years of age, followed by a further fivefold decrease by 13 years, at which point neurons also appeared more mature than those seen in samples from younger brains. The authors observed only about 2.4 new cells per square millimeter of DG tissue in early adolescence, and found no evidence of newborn neurons in any of the 17 adult post-mortem DG samples or in surgically extracted tissue samples from 12 adult patients with epilepsy.