Evidence for Adult Neurogenesis in Humans Even in Very Late Life
The past year or so has seen an energetic debate over whether or not new neurons are generated in the adult human brain, a process known as neurogenesis. This process is well known and well studied in mice, and thought to be very important in the resilience and maintenance of brain tissue. The human data has always been limited, however, due to the challenges inherent in working with brain tissue in living people, and it was assumed was that the mouse data was representative of the state of neurogenesis in other mammals. In this environment, the publication of a careful study that seemed to rule out the existence of neurogenesis in adult humans produced some upheaval, and spurred many other teams to assess the human brain with greater rigor than was previously the case.
So far, all of the following studies published so far do in fact show evidence of adult neurogenesis in humans. This is the better of the two outcomes, as the regenerative medicine community has based a great deal of work on the prospect of being able to upregulate neurogenesis in order to better repair injuries to the central nervous system, or partially reverse the decline of cognitive function in the aging brain. The study here is particularly reassuring, as it shows that even in very late life there are signs that new neurons are being generated in the brain.
The idea that new neurons continue to form into middle age, let alone past adolescence, is controversial, as previous studies have shown conflicting results. A new study is the first to find evidence of significant numbers of neural stem cells and newly developing neurons present in the hippocampal tissue of older adults, including those with disorders that affect the hippocampus, which is involved in the formation of memories and in learning. Researchers also found that people who scored better on measures of cognitive function had more newly developing neurons in the hippocampus compared to those who scored lower on these tests, regardless of levels of brain pathology.
The researchers think that lower levels of neurogenesis in the hippocampus are associated with symptoms of cognitive decline and reduced synaptic plasticity rather than with the degree of pathology in the brain. For patients with Alzheimer's disease, pathological hallmarks include deposits of neurotoxic proteins in the brain. "In brains from people with no cognitive decline who scored well on tests of cognitive function, these people tended to have higher levels of new neural development at the time of their death, regardless of their level of pathology. The mix of the effects of pathology and neurogenesis is complex and we don't understand exactly how the two interconnect, but there is clearly a lot of variation from individual to individual. The fact that we found that neural stem cells and new neurons are present in the hippocampus of older adults means that if we can find a way to enhance neurogenesis, through a small molecule, for example, we may be able to slow or prevent cognitive decline in older adults, especially when it starts, which is when interventions can be most effective."
The researchers looked at post-mortem hippocampal tissue from 18 people with an average age of 90.6 years. They stained the tissue for neural stem cells and also for newly developing neurons. They found, on average, approximately 2,000 neural progenitor cells per brain. They also found an average of 150,000 developing neurons. Analysis of a subset of these developing neurons revealed that the number of proliferating developing neurons is significantly lower in people with cognitive impairment and Alzheimer's disease. The scientists are now interested in finding out whether the new neurons discovered in the brains of older adults are behaving the way new neurons do in younger brains.