MMD 1/27: Neurogenesis and Stem Cell Applications in Neurology

Stem Cells and Neurogenesis in Neurological Disorders

  • Application of Stem Cells:

    • Stem cells can be utilized to counteract neurodegeneration in various neurological disorders, including Alzheimer’s disease.

    • Example discussed includes comparing normal brain cells to those affected by Alzheimer’s, highlighting cell loss in affected areas.

  • Therapeutic Strategies:

    • A therapeutic strategy involves stimulating neurogenesis in areas where cells have degenerated.

    • Goal: Replace lost neurons with newly generated cells to fill empty areas of the brain.

    • This requires the injection of genes into specific brain areas to stimulate neurogenesis.

  • Challenges in Neurogenesis:

    • Regenerated cells (neurons) must integrate properly:

    • Need to develop axons and synapses appropriately.

    • Must reach correct functional areas to ensure viability and utility in treatment.

    • Past research shows promise with animal models, but results do not translate effectively to human applications.

  • Factors in Neurodegeneration Treatment:

    • In addition to cell count, differentiation status is critical for developing effective treatment strategies for neurodegeneration.

    • This emphasizes the need for successful recruitment of new cells into the damaged areas.

    • Visual modifications to existing tissues can allow for amplification and direct injection of cultured cells into damaged areas without needing recruitment.

  • Neurogenic Niches:

    • Neurogenic areas are regions in the brain such as the hippocampus and the ventricular zone that are vital for neurogenesis.

    • Cells can be stimulated to migrate to these niches for regeneration purposes.

  • Neuronal Development Stages:

    • Neurogenesis: Initial stem cell proliferation phase.

    • Neuronal Migration: New neurons migrate to their designated final destinations in the brain.

    • Synapse Formation: Final stage where new neurons form synapses to connect with existing neural networks.

  • Types of Neuronal Migration:

    • Radial Migration:

    • Neurons originating from the ventricular zone move radially to their final location, typically resulting in excitatory pyramidal neurons.

    • Tangential Migration:

    • Neurons migrate horizontally from regions such as the medial and lateral ganglionic eminences, often resulting in inhibitory interneurons.

  • Layering in Neurons:

    • The developing brain consists of six layers:

    1. Layers 1 and 2 contain newer cells.

    2. Layers 5 and 6 are older cells, demonstrating a unique inside-out position during and following radial migration.

  • Excitation/Inhibition Balance (EI Balance):

    • Essential for proper brain function:

    • Pyramidal neurons (excitatory) and interneurons (inhibitory) maintain this balance.

    • Imbalances can lead to neurodevelopmental or psychiatric conditions.

  • Neuronal Migration Mechanism:

    • Neurons extend a leading process that guides migration, supported by a central zone that carries the nucleus.

    • Proteins like Myosin play a role in this migration process. Any mutation affecting these proteins can compromise neuronal migration, which can lead to developmental disorders.

  • Impact of Migration Defects:

    • Defective migration can lead to conditions such as autism, intellectual disabilities, schizophrenia, and cerebral palsy due to disrupted connectivity among neurons.

  • Neuronal Structure and Health:

    • Unique structural arrangements support functional neuronal connectivity.

    • Columnar structures in the brain relate to connectivity, and disruption is seen in various pathologies, including autism and Alzheimer’s.

  • Postnatal Brain Development and Migration:

    • Although migration primarily occurs pre-birth, some limited postnatal migration and neurogenesis can occur, especially in the hippocampus for adults.

    • Evidence shows significant migration in infant brains, but postnatal migration is generally restrictive.

  • Experimental Evidence:

    • Studies illustrate precise mechanisms of migration and the resulting structural features, shedding light on the importance of specific genes and proteins that guide migration processes.

    • Issues like LIS1 gene mutations result in disrupted neuronal migration, causing significant structural and functional brain disorders.