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.”
