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Specific Trophic Factor ‐ Receptor Interactions: Key Selective Elements in Brain Development and “Regeneration”

An hypothesis is presented which emphasizes the key role of specific trophic factor-receptor interactions in the development of the brain. We postulate that very early in development neurons become dependent on external factors (mainly neuropeptides) for guidance and survival. These requirements are the key to the selection process which results in the creation of a functional nervous system. These specific localized trophic factor requirements are postulated to persist throughout life. Disruptions in specific trophic factor-receptor systems are postulated to be responsible for a variety of age-related neurodegenerative diseases. The implications of recent animal and human transplant experiments in the context of the theoretical framework discussed above are profound. It would appear that the mature mammalian brain possesses an exquisite ability to regenerate specific connections to replace those lost due to death or injury to nerve cells. Unfortunately, it does not contain a population of undifferentiated stem cells to supply the necessary healthy neurons. The reason for this appears obvious based on the theoretical considerations given above, that the specific trophic factor-receptor interactions needed to produce a functional brain circuitry are necessarily stringently selective. Therefore, a significant stem cell population does not survive. However, if an appropriate stem cell population, ie, a fetal transplant, is provided, the brain will "heal itself" according to the program outlined above. In the future it may be technically feasible to perform genetic testing of newborns to determine to which genetic neurological diseases they are susceptible and at an appropriate time provide the appropriate fetal transplant. Obviously, society will have to deal with the profound ethical questions this technology will raise.