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Neurogenesis in the adult human hippocampus

Neurogenesis in the adult human hippocampus. Eriksson et al. (collab. With Gage) Presented by Akash Chandawarkar. 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

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Neurogenesis in the adult human hippocampus

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  1. Neurogenesis in the adult human hippocampus Eriksson et al. (collab. With Gage) Presented by Akash Chandawarkar

  2. 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)

  3. The Big Question Does neurogenesis occur in the HUMAN adult brain?

  4. Using Bromodeoxyuridine (BrdU) • Thymidine analog • Incorporates into S-phase of replicating DNA • Antibody detection against BrdU • Carcinogenic due to mutagenic properties

  5. Methods • Cancer patients (n=5) 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

  6. Results – Fig. 1

  7. Results – Fig. 2

  8. Results – Fig. 4

  9. Results – Fig. 5

  10. 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

  11. 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

  12. 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

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