Genetics of Childhood Disorders: XXXVI. Stem Cell Research, Part 1: New Neurons in the Adult Brain

Abstract

Until recently, it was assumed that neurogenesis, or the production of new neurons, occurs only during development and never in the adult organism. The famous neuroanatomist Cajal stated that “Once development was ended, the fonts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed and immutable: everything may die, nothing may be regenerated.” This statement holds true for most of the regions of the adult brain. However, there are two adult brain areas in which neurogenesis is observed: the subventricular zone of the anterior lateral ventricles gives rise to cells that become neurons in the olfactory bulb, and the subgranular zone in the dentate gyrus generates new granule cell neurons in the hippocampus, a brain region that is important for learning and memory. The initial studies that suggested that the adult brain could generate new neurons were largely ignored. In the 1960s Joseph Altman and coworkers published a series of papers reporting that some dividing cells in the adult brain survived and differentiated into cells with morphology similar to neurons. They used tritiated thymidine autoradiography to label the cells. Tritiated thymidine is incorporated into the DNA of dividing cells. They found that the highest density of labeling was in the subventricular zone and in the dentate gyrus of the hippocampus. It was known that the dentate gyrus of the hippocampus is essentially devoid of glia. Therefore, Altman attributed the labeling in this region to the uptake of thymidine by dentate granule cells. However, he could not prove that the adult-generated cells were neurons rather than glia, since no phenotypic markers were available that could be used in conjunction with thymidine autoradiography. The absence of specific markers for neurons and glia and continued skepticism surrounding the novel concept of adult neurogenesis limited further development of the research. In the mid 1970s and the early 1980s, Michael Kaplan and his colleagues reexamined the initial observations using the electron microscope and added substantial confidence that neurogenesis could occur in the adult brain. Combining electron microscopy and tritiated thymidine labeling, they showed that