NEUROGENESIS IN THE DENTATE GYRUS OF THE ADULT TREE SHREW IS REGULATED BY PSYCHOSOCIAL STRESS AND NMDA RECEPTOR ACTIVATION

These studies were designed to determine whether adult neurogenesis oc curs in the dentate gyrus of the tree shrew, an animal phylogeneticall y between insectivores and primates, and to explore the possibility th at this process is regulated by stressful experiences and NMDA recepto r activation. We performed immunohistochemistry for cell-specific mark ers and the thymidine analog bromodeoxyuridine (BrdU), a marker of DNA synthesis that labels proliferating cells and their progeny, on the b rains of adult tree shrews subjected to psychosocial stress or NMDA re ceptor antagonist treatment. Cells that incorporated BrdU in the denta te gyrus of adult tree shrews were primarily located in the subgranula r zone, had morphological characteristics of granule neuron precursors , and appeared to divide within 24 hr after BrdU injection. Three week s after BrdU injection, BrdU-labeled cells had neuronal morphology, ex pressed the neuronal marker neuron specific enolase, and were incorpor ated into the granule cell layer. Vimentin-immunoreactive radial glia were observed in the dentate gyrus with cell bodies in the subgranular zone and processes extending into the granule cell layer. Exposure to acute psychosocial stress resulted in a rapid decrease in the number of BrdU-labeled cells in the dentate gyrus. In contrast, blockade of N MDA receptors, with the NMDA receptor antagonist MK-801, resulted in a n increase in the number of BrdU-labeled cells in the dentate gyrus. T hese results indicate that adult neurogenesis occurs in the tree shrew dentate gyrus and is regulated by a stressful experience and NMDA rec eptor activation. Furthermore, we suggest that these characteristics m ay be common to most mammalian species.