Hippocampal neurogenesis in adult Old World primates - PubMed (original) (raw)

Hippocampal neurogenesis in adult Old World primates

E Gould et al. Proc Natl Acad Sci U S A. 1999.

Abstract

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.

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Figures

Figure 1

Figure 1

Photomicrographs (A and B) and confocal laser scanning microscopic images (C_–_F) depicting new cells produced in the adult monkey brain. BrdUrd-labeled cells were observed in the granule cell layer of the dentate gyrus (A) (arrows) (animal 7) and in a region corresponding to the rostral migratory stream in rodents (B) (arrows) (animal 4). (C) Clusters of BrdUrd-labeled cells (blue nuclear stain) were observed in the subgranular zone of the dentate gyrus (arrows) (animal 2). Many of these clustered cells in animals injected with BrdUrd followed by short survival times (2 hr after BrdUrd injection) were not immunoreactive for NSE (green cytoplasmic stain). (D) In monkeys perfused 1–2 weeks after the last BrdUrd injection, BrdUrd-labeled cells expressing the neuronal marker NSE were observed (arrow is an example from animal 3). (E) BrdUrd-labeled cells in the granule cell layer of animals perfused 2 weeks after the last of five BrdUrd injections were immunoreactive for NeuN (arrows indicate double-labeled cells) (animal 1). (F) TOAD-64 stained cells with the morphology of granule cells were observed in the granule cell layer (arrows) (animal 1) (granule cells stained here with the DNA dye Hoechst 44323) gcl, granule cell layer. [Bars = 30 μm (A), = 15 μm (B), = 10 μm (C, D, and E), and = 40 μm (F).]

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