In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain.

It has traditionally been held that the adult brain is incapable of significant self-repair, due in part to its inability to generate new neurons. Nevertheless, rodents and birds have been found to harbor neural precursor cells in adulthood. We asked whether the adult human brain might retain such precursors, by culturing samples of temporal lobe under conditions permissive for neuronal differentiation, while exposed to 3H-thymidine. Adult human temporal lobe cultures, derived from cortex, subcortex, and periventricular subependymal zone (SZ), were incubated for 7-28 d, stained for neuronal and glial antigens, and autoradiographed. Neuron-like cells were found in explant outgrowths and monolayer dissociates of SZ and periventricular white matter, but not cortex; they expressed neuronal antigens including MAP-2, MAP-5, NF, and N-CAM, and were GFAP-. Neurons responded to K+ depolarization with rapid and reversible increases in intracellular Ca2+, with much greater increments than those noted in glia. Although most neurons were not 3H-thymidine labeled, a small number of MAP-2+ and MAP-5+/GFAP- cells did incorporate 3H-thymidine, suggesting neuronal production from precursor mitosis. Rare 3H-thymidine+ neurons were also found in cultures of subventricular white matter; in these, GFAP+ astrocytic mitogenesis was common, while O4+ oligodendrocytes, although the predominant cell type, were largely postmitotic. Thus, the adult human forebrain harbors precursor cells that retain the potential for neuronal production and differentiation in vitro.