Neurogenesis in the adult human hippocampus

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Neurogenesis in the adult human hippocampus

• Eriksson et al. (collab. With Gage)
• Presented by Akash Chandawarkar

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Prior State of the Field Neurogenesis

• Loss of neurons in adult brain devastating ? no
  newly dividing cells
• Inability to replace cells in disease and
  impairment
• Growing body of interesting evidence
• Mice, rat, guinea pig, rabbit, monkey
• Generation of granule neurons
• Subventricular zone of lateral ventricles
• Subgranular zone of dentate gyrus (hippocampus)

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The Big Question

• Does neurogenesis
• occur in the HUMAN adult brain?

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Using Bromodeoxyuridine (BrdU)

• Thymidine analog
• Incorporates into S-phase of replicating DNA
• Antibody detection against BrdU
• Carcinogenic due to mutagenic properties

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Methods

• Cancer patients (n5) received IV infusion of
  BrdU for diagnostic purposes
• Postmortem tissue slices of dentate gyrus and
  subventricular zone
• Immunohistochemistry analysis
• BrdU (labeled cells)
• Neuronal markers ? NeuN, calbaldin, NSE
• Astroglial marker ? GFAP

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Results Fig. 1
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Results Fig. 2
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Results Fig. 4
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Results Fig. 5
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Conclusions

• New neurons are generated in the adult brain
• Dentate gyrus, CA4 hillus, SVZ
• Progressive death of newly generated cells over
  time (?)
• Newly generated cells migrate and then
  differentiate into specific cell types

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Implications

• Constitutive birth of new neurons in human brain
  ? goes against old dogma
• Cellular basis for plasticity/self-repair
• Potentials for cellular neurosurgery
• Directed differentiation of neural progenitors
• Replacement of damaged neural circuits in
  neurodegenerative diseases

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The role of neurogenesis

• Important for learning and memory
• Regulation of stress
• Decrease during physiological or psychological
  stress
• Increase during exercise
• Decrease in depression ? antidepressants
• Induction of adult neurogenesis in other parts of
  the brain