Adult Neurogenesis 4

Historical Perspective on Adult Neurogenesis

  • Ramon y Cajal: Pioneer in neuroscience; developed techniques to label and map neurons. Observed that adult brains appear to lack dividing cells.
  • The Dogma of No Adult Neurogenesis: Suggested that once development ends, no new neurons form in adults; this belief persisted into the 1900s.

Breakthroughs in Neurogenesis Research

  • Joseph Altman (1960s): Injected thymidine analogues in mice to identify dividing cells. Found new neurons generated in the adult brain at:

    • Lateral wall of the lateral ventricles.
    • Dentate gyrus, though his findings were initially met with skepticism and controversy.

  • Fernando Nottebohm (1980s): Studied zebra finches learning songs. Found neurogenesis in the High Vocal Center, supporting neurogenesis relevance for learning and memory.

  • Led to usage of techniques like immunohistochemistry to further understand stem cell markers (e.g., vimentin).

Locations of Adult Neural Stem Cells

  • Neural stem cells generally line the ventricles in most vertebrates (similar structure as in development).
  • Unique to Mammals: The dentate gyrus where stem cells are located away from the ventricle.
  • Great Regeneration Capacity: Found in organisms like newts and some fish where stem cells are reactivated after injury.

Neurogenesis Specifics in Mammals

  • Two Main Sites:
    • Subventricular Zone (SVZ):
    • Contains B cells (quiescent neural stem cells) that produce C cells (intermediate progenitor cells), leading to A cells (neuroblasts) that migrate to the olfactory bulb.
    • Details:
      • Neurons in the olfactory bulb generated from SVZ divide and become mature inhibitory neurons involved in smelling.
    • Dentate Gyrus:
    • Neural stem cells have radial glial-like morphology producing astrocytes and granule neurons.
    • Neurogenesis contributes to learning, memory, and pattern separation.

Activation and Effects of Neurogenesis

  • Enriched Environment: Running increases neural stem cell proliferation in studies, leading to new neurons, primarily influenced by environmental stimuli.
  • Factors Influencing Neurogenesis:
    • Age (decreases with age), Alzheimer's disease (reduced proliferation in dentate gyrus), depression, stress (lowers neurogenesis).

Neurogenic Niche

  • This environment provides support for neurogenesis, including:
    • Endothelial cells (blood vessels), astrocytes, microglial cells, and existing neurons. These factors influence neural stem cell behavior and proliferation.

Adult Neurogenesis Measurement Challenges

  • Difficulties in human studies include:
    • Tissue acquisition and analysis techniques; potential carcinogenic substances like thymidine analogues are no longer used.
    • Use of Carbon-14 Dating: Utilizes changes in atmospheric carbon levels post-atomic bomb tests to determine neurogenesis periods in dentate gyrus.

Ongoing Controversies and Learnings

  • A study (2018) indicated very few proliferating cells in adult human dentate gyrus, raising questions about adult neurogenesis.
  • Importance of precise tissue handling and newer methodologies (e.g., single-cell RNA sequencing, machine learning) to identify stem cells amid astrocytes.

Conclusion: Current Understanding and Future Directions

  • Adult neurogenesis occurs predominantly in two areas in mammals: the SVZ and dentate gyrus, particularly significant in learning, memory, and response to stress.
  • Key Takeaways: Exercise and enriched environments can enhance neurogenesis, offering potential strategies for health and cognitive function.