How can we rebuild the brain when it has been affected by disease or age? There are two possible ways to develop new brain cells:
1) Cells relocated or generated from within the individual. The advantage of this strategy is that it is less invasive, you don’t have to deal with immunological problems of compatibility, and it is parsimonious with the body’s existing framework. These cells are called endogenous.
2) Cells from an outside source (such as a donor) and transplanted into the individual. the advantage here is that larger numbers can be obtained, different sources can be used (embryonic and adult stems cells, or even one day some sort of synthesis), and the state of the cell before differentiation can be optimized outside of the brain. These cells are called exogenous.
How can we stimulate more neurogenesis within the brain?
There is evidence that many factors which contribute to neurogenesis in vitro also contribute to neurogenesis in vivo, including epidermal growth factor and basic fibroblast growth factor-2. The process is regulated physiologically by glucocorticoids, sex hormones, growth factors, excitatory neurotransmission, learning, and stress. It can be stimulated by certain drugs, such as lithium, antidepressants (that may be why they work), antipsychotics, NMDA antagonists, phosphodiesterase inhibitors, and anti-inflammatories.
Injury is also one of the main contributors to neurogenesis in the adult brain, and there are a number of potentially useful applications based on this process. In stroke-induced neurogenesis, the new cells were found in areas not directly affected by injuries themselves, which means that there must be a mechanism to couple neurogensis with injury across the brain. Also, an injury to one half of the brain produced neurogenesis on both sides of the brain, implying that there may be some central part of the brain regulating neurogenesis that is blind to the actual location but still able to recognize which functions are impaired.
If we could tap into this endogenous system to repair regions that have not yet been damaged (or regions that have been damaged by disease but not injury), we could exploit our body’s own system to help repair ourselves. There is no such thing as a free lunch, but the most detrimental effect of such action might be for the brain to simply consume more energy. This may have been a limiting factor in the Paleolithic era in which human ancestors evolved, but we have plenty of food and nutrients to go around in most areas of the industrialized world.
One of the most important questions is how well these neurons integrate into the existing framework of the brain. Some studies have been done to touch upon this question, but it is still a relatively open question and without its affirmative answer all of this work may be for naught. Of course, it doesn’t make much sense for the body to waste energy on neurogenesis if it doesn’t accomplish anything.
But even if the natural amount of neurogenesis is unable to procure an effect, it is possible that a supraphysiological level could be reached from growth factors, drugs, or some combination that would provide us with methods for using adult neurogenesis clinically.
Greenburg DA, Jin K 2007 Regenerating the brain. International Review of Neurobiology 77: 1-22. doi: 10.1016/S0074-7742(06)77001-5.