Can neurons regenerate? Are the brain and spinal cord nerve cells able to repair themselves or replicate? This is a topic that has received more attention in the past decade than it enjoyed in the previous 50 years. To appreciate this some historical review is in order.
But first, here’s a story to begin this section. Recently, in 2006, Dr. Michael Fehlings extracted adult stem cells, not embryonic fetal stem cells, from adult rats and injected them into the spinal cords of rats that had had their spinal cords crushed. He found that when he treated these “implanted” rats with a cocktail of human growth hormone, and minocycline, these rats were able to make new myelin sheaths around the nerve fibers which restablished the ability of the nerves to conduct their signals from the brain to the muscles of the limbs. The rats were able to again bear weight on their legs (and arms) and to walk with better coordination. The implanted adult stem cells had become new perineural cells which made and repaired the myelin. We didn’t think this was possible.
Dr. Joseph Altman, using a relatively new technology in the 1960’s, injected animals with radioactive thymidine and looked for its presence in neurons. Its presence would denote the formation of new DNA sequences and therefore, by extension, new cells. And indeed he found it. However, as is often the case with such discoveries that call into question basic tenets of science and utilize novel methodologies, his findings were largely ignored.
The concept of the static brain gathered momentum with the research of Dr. Pasko Rakic at Yale. In the 1980’s he used much the same technique used by Dr. Altman at MIT, radioactive thymidine labeling of new neurons in primates. However, unlike Dr. Altman, he was unable to identify any uptake of thymidine in his primate model. This result appears to have confirmed Dr. Cajal’s findings more than a half century before and scientists were satisfied that in the adult mammal no neurogenesis occurs.
Since the mid 1990’s, however, more and more data from well designed studies has begun to accumulate. Dr. Ronald Duman has demonstrated the propagation of trophic and growth factors (brain derived growth factor or BDGF) which result from brain tissue exposure to antidepressants such as fluoxetine and other SSRI antidepressants. These trophic factors stimulate neurogenesis by 50% in the hippocampus of the rat. Dr. Duman believes this observation may account for the 7-14 day delay in the clinical benefits of antidepressant medications and that the effects of the medications are dependent on the generation of new neurons rather than exclusively on the inhibition of the reuptake of serotonin. He has also demonstrated that stress decreases these same trophic factors which are stimulated by exposure to fluoxetine.
Dr. Elizabeth Gould has data in primates that shows when they are exposed to novel environments, the hippocampal neuron count increases dramatically, but under stressful conditions for prolonged periods of time, the count decreases. Additionally, in the novel environment, the dendritic number and density increases. This may account for the different findings of Rakic in whose studies the primates were not constantly exposed to novel environmental stimuli.
To add even more support to the concept of neurogenesis in the adult mammalian brain, Dr. Jonas Frisen published a paper in 1999 identifying stem cells in the brain. These adult stem cells are stimulated to differentiate into neurons by a cascade of proteins and trophic factors. Dr. Frisen is working to identify drugs that might trigger this cascade and subsequent differentiation of adult stem cells, specifically in the substantia nigra of a rat model of Parkinson’s disease. He has data to show a reversal of limb paralysis after 5 weeks of treatment with one of his drugs suggesting a restoration of dopamine neurons in the brains of these animals.
So by way of review, since 1995 the field of neuroscience has progressed from a belief that was spawned at the turn of 1900 by Dr Cajal’s papers postulating the absence of neurogenesis in the adult mammalian brain to the demonstration of the presence of adult stem cells in the mammalian brain which are capable of differentiating into new neurons as a result of stimulation of the trophic protein cascade by certain drugs and chemicals and that then can be integrated into the brain’s functional network.
And why wouldn’t this be the case? After all, mammals have stem cells in every tissue. Erythropoesis is probably the best known example of adult stem cell differentiation and it is stimulated by erythropoietin, a hormone, and by L-carnitine, and by taurine, and by somatotropin or human growth hormone, to name only a few. Dermis and endothelial tissues regenerate similarly and can be stimulated to do so by specific hormones and chemicals such as basic fibroblast growth factor or BFGF that appear to drive the cascade of trophic proteins responsible for this differentiation.