Proliferative status of cells in adult human dentate gyrus

Abstract

Experiments in rodents and marmoset monkeys indicate that granule neurons of the dentate gyrus may be renewable throughout the entire life of the animal. Whether this occurs in larger primates remains a matter of contention. However, a recent study of brain samples from five adult humans who had been injected with the thymidine analog bromodeoxyuridine indicates that new neurons might indeed be produced in the dentate gyrus. In this study, hippocampus specimens removed from 18 adult humans for treatment of epilepsy were examined. The cell cycle marker Ki67, which is expressed from late G1 to M phase, was demonstrated by immunohistochemistry, and H2b/H3/H4 histone mRNAs, which are expressed during S phase, were demonstrated by in situ hybridization. Only 0.17% of cells in the subgranular layer, the site of neuronal progenitor cells, were Ki67 immunoreactive but the identity of these could not be proven. Although the histone in situ hybridization technique was shown to work in human fetal brain, no M phase cells could be demonstrated in the hippocampus. The generation of new granule neurons in the human hippocampus must occur at a very slow rate. The approaches used in this study are likely unsuitable for studying cell populations with low turnover rate. Further work is needed to determine the fate of newly generated cells in the dentate gyrus. This information is of importance to our understanding of the mechanisms of learning and memory.