Neurogenesis in the Dentate Gyrus of the Adult Tree Shrew Is Regulated by Psychosocial Stress and NMDA Receptor Activation By Elizabeth Gould, Bruce McEwen, Patima Tanapat, Lisa Galea, & Eberhard Fucha

Tree Shrew

What is ??? Tree shrews (Tupaia belangeri) are considered to be phylogenetically between insectivores and primates. Neurogenesis occurs throughout life, and occurs when new neurons and glial cells are born in the brain. Bromodeoxyuridine (BrdU) was used as a good test for neurogenesis because BrdU is incorporated into dividing cells.

Methods Experiment 1: The dentate gyrus of tree shrews were processed for BrdU ICC at 2 and 24 hour survival times (n = 3 for each group) after BrdU injections. The 2 hour survival time allowed for BrdU uptake into cells synthesizing DNA and the 24 hour survival time allowed for the completion of at least one cell cycle by cells in S phase at the time of BrdU injection. Experiment 2: To determine if cells the incorporate BrdU survive and express the neuronal marker neuron specific enolase (NSE). BrdU injection and perfused transcardally 3 weeks later (n = 3 for each group) after BrdU injections.

Methods Continued.. Experiment 3: To determine if cell proliferation can be modulated by a stressful experience. Acute psychosocial stress in the form of active competition for an enlarged territory and the establishment of dominant/subordinate relationship. The acute psychosocial stress occurred for a total of 1 hour. The stressed group and the control unstressed group of animals were given one BrdU injection each with a 2 hour survival time (n = 3 for each group) after BrdU injections.

Methods Continued… Experiment 4: To determine if the production of cells in the dentate gyrus are affected by NMDA receptor activation. Animals were injected with a specific noncompetitive NMDA receptor antagonist MK-801 or saline. The MK-801group and the saline group of animals were given one BrdU injection each with a 2 hour survival time (n = 3 for each group) after BrdU injections.

This Study… The present studies were undertaken to determine whether granule cell production and its regulation by stressful experience and excitatory input occur in the dentate gyrus of the adult tree shrew Tupaia belangeri.

Data Analysis For each brain, at least six sections were selected for analysis from middle to caudal dentate gyrus. For each section, cells in the dentate gyrus were counted and the means of the data were subjected to a Student’s t test.

Data Analysis Table

Cell Types in the DeNtate Gyrus

Results BrdU labeled cells were found throughout the dentate gyrus at all levels examined (Figs 1-3). ~85% of the cells had the morphological characteristics of granule cell precursors (round or oval), medium sized cell bodies (Fig. 4). The rest of the cells had the morphological characteristics of glial cells (triangular or irregular), small sized cell bodies (Fig. 4). Typically these cells were found (Figs. 1-4): a. subgranular zone (sgz) b. border of the granule cell layer (gcl) c. hilus

Results Continued… Quantitative Analysis revealed 2 times as many BrdU labeled cells between 2 and 24 hour survival times after BrdU injections: All of the cells that were labeled with BrdU and NSE were located in the gcl (Figs. 1-3) and had the morphological characteristics of granule neurons. Exposure to a single episode of acute psychosocial stress that last 1 hour resulted in a significant decrease in the density of BrdU-labeled cells in the dentate gyrus compared to the unstressed controls. Treatment with the NMDA receptor antagonist MK-801 resulted in a significant increase in the density of BrdU-labeled cells in the dentate gyrus.

Figure 1

Figure 2

Figure 3

NMDA Receptor

Stress Related Diseases

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