Hippocampal neurogenesis in adult Old World primates
The production of new hippocampal neurons in adulthood has been well documented in rodents. Recent studies have extended these findings to other mammalian species, such as tree shrews and marmoset monkeys. However, hippocampal neurogenesis has not been demonstrated in adult Old World primates. To investigate this possibility, we injected 11 adult Old World monkeys of different ages (5–23 years) with the thymidine analog bromodeoxyuridine and examined the fate of the labeled cells at different survival times by using neuronal and glial markers. In the young-adult and middle-aged monkeys, we found a substantial number of cells that incorporated bromodeoxyuridine and exhibited morphological and biochemical characteristics of immature and mature neurons. New cells located in the dentate gyrus expressed a marker of immature granule neurons, Turned On After Division 64 kDa protein, as well as markers of mature granule neurons including neuron specific enolase, neuronal nuclei, and the calcium-binding protein calbindin. Fewer new cells expressed the astroglial marker glial fibrillary acidic protein. Evidence of neurogenesis was observed in the oldest monkeys (23 years) as well, but it appeared to be less robust. These results indicate that the adult brains of Old World monkeys produce new hippocampal neurons. Adult macaque monkeys may provide a useful primate model for studying the functional significance of adult neurogenesis.
A hallmark of many neurodegenerative diseases in humans is the permanent loss of neurons. The human brain is generally believed incapable of producing new neurons to repair damaged areas in adulthood. The key to stimulating neurogenesis in damaged brain regions may lie in studying the systems that continue to produce new neurons throughout life. In adult birds, extensive neurogenesis has been observed in both the song system and in the hippocampal formation (1–3). In rodents, the production of new neurons in adulthood has been reported in two brain regions, the hippocampal formation and the olfactory bulb (4–8). Recent evidence has shown that two other mammalian species, tree shrews and marmoset monkeys, produce hippocampal granule neurons in adulthood (9, 10), and most recently, this phenomenon has been demonstrated in humans (11). Although the existence of this process is intriguing, the function of new neurons in the adult brain remains enigmatic. However, there is no Old World primate animal model in which to study adult neurogenesis. Indeed, previous studies using 3H-thymidine autoradiography reported no neurogenesis in the brains of adult Old World monkeys (12, 13). We reexamined this possibility by using bromodeoxyuridine, a thymidine analog, and report here that a substantial number of hippocampal neurons are indeed produced in the brains of adult Old World monkeys.