Neurogenesis in the Dentate Gyrus of the Adult Tree Shrew Is Regulated by Psychosocial Stress and NMDA Receptor Activation

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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

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Tree Shrew
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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.

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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.

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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.

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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.

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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.

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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 Students t test.

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Data Analysis Table
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Cell Types in the DeNtate Gyrus
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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

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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.

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Figure 1
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Figure 2
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Figure 3
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NMDA Receptor
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Stress Related Diseases
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Thank You