Residue from Nuclear Bomb Testing Shows That Contrary to Earlier Reports, Neurogenesis Occurs in the Brains of Adults
In 2013 we reported that according to Pasco Rakic, professor of neuroanatomy at Yale University, neurogenesis (the production of new neurons) occurs only in rodents, and not in any significant amount in the brains of adult primates. However, a new carbon-dating procedure shows that the adult human brain does actually continue to create new neurons.
According to an article by Spalding et al. published more recently in the journal Cell, such neuroplasticity occurs to a much greater degree than previously thought. The authors base their research on levels of carbon isotope 14 (14C) that were released into the atmosphere during aboveground nuclear bomb tests between 1945 and 1963. Dividing cells require carbon, so the 14C released into the atmosphere during the era of nuclear testing made its way into the cells of people who were alive at the time. Levels of 14C that were incorporated into the DNA of dividing cells correlate with levels of 14C in the atmosphere at the time the cells divided, and since carbon levels have declined at a predictable rate since the nuclear tests, measuring the 14C in cells can show how old they are.
Spalding et al. show that neurogenesis in humans occurs only in the hippocampus. They found evidence that a subpopulation of hippocampal neurons continually renews itself at a rate of about 700 new neurons per day, while other hippocampal cells are non-renewing. The annual turnover rate of about 1.75% is the same for men and women and declines slightly with age.
The researchers were able to determine that the renewing cells play an important role in certain types of brain function. Long-term potentiation, the process by which learning and memory can occur, depends heavily on new cells produced in the part of the hippocampus knows as the dentate gyrus.
The Myth of Neurogenesis in Adult Primates Debunked
In a plenary lecture at the Collegium Internationale Neuro-Psychopharmacologicum (CINP) in Istanbul in 2012, Pasco Rakic, professor of neuroanatomy at Yale University, may have debunked a myth of modern medicine, one that we have cited in many previous BNNs. Despite what has been written by famous neuroscientists and published in the most prestigious journals, including Science, Cell, and PNAS, based on data in rodents, Rakic presented evidence that neurogenesis does not occur to any substantial extent in adult primates.
Two decades ago, data in rodents and other species clearly indicated that neurogenesis, the creation of new neurons, occurred in adult animals, especially in the dentate gyrus of the hippocampus. Thousands of papers were written on the subject, and neurogenesis was understood to be possible in adult humans as well. It was even suggested based on data in rodents that the mechanism of action of antidepressants was dependent on neurogenesis. However, Rakic argues that most of the research on neurogenesis was based on faulty data.
Rakic found that while rats do have neurogenesis into adolescence, it diminishes greatly in older adult animals. In primates, neurogenesis in the cortex ends before birth. In the primate dentate gyrus of the hippocampus, there is some postnatal neurogenesis, but it rapidly drops toward zero in the first months of life. Rakic concludes: “We are as old as our neurons…or slightly younger.”
Why should primates have permanent stores of neurons when rodents and other lower animal species get new ones further into their lifespan? Rakic postulates that for primates, neurons must hold experience-dependent memories necessary for the survival of the species, and turning them over would endanger the permanence of this memory. Whatever the reason, it is disappointing to find out that the revolutionary discovery of adult neurogenesis in rodents so widely presumed to also occur in adult primates and humans may not be correct.
This has clinical implications. If we don’t get replacement hippocampal neurons like rats do, it is even more important to protect the billions of neurons that we do have. There are many things that endanger neurons, including inflammation, oxidative stress, high cortisol, poor diet, psychosocial adversity, and episodes of depression and mania. Greater numbers of mood episodes are associated with increasing degrees of cognitive dysfunction because of these many factors. A startling statistic from Denmark by Lars Kessing is that having four or more hospitalizations for depression (either unipolar or bipolar) doubles the risk for a diagnosis of dementia in late life. Thus, it looks like too many episodes hurt the brain.
However, on the positive side, the mood stabilizers (lithium, lamotrigine, valproate, and carbamazepine) and some atypical antipsychotics prevent episodes and increase the neuroprotective factor BDNF, or brain-derived neurotrophic factor, which facilitates synaptogenesis and helps protect neurons. BDNF is produced in selected neurons in the brain and decreases with stress and affective episodes, further endangering neurons. Since many effective treatments both prevent episodes and their associated decreases in BDNF and also directly increase BDNF, they may be having a dual positive benefit. The evidence is best for lithium having neuroprotective effects that can be directly observed in humans. Thus a not unreasonable mantra for patients with recurrent mood disorders is: “Prevent Episodes, Protect the Brain.”
