L14- Neurogenesis Flashcards
How do neural stem cells differentiate?
Neural stem cell
Lineage restricted progenitor cell
Oligodendrocyte, astrocyte, neuron
What is the potency of neural stem cells?
Multipotent- tissue types within neural tissue only
What are the NSC markers in vivo?
• Earliest- SOX(2) genes in neural plate
• Late- Nestin (intermediate filament protein)
• RNA- binding protein Musasti
Appear after SOX proteins and persist in adult NSC
How are dividing/newborn cells identified?
- BrdU labelling- integrate DNA with BrdU and detect using antibody
- Retroviral labelling- vector only integrates in DNA of divding cells, detected using GFP it is expressed all over cells
What regions is adult neurogenesis restricted to?
Subventricular zone of the lateral ventricles
Subgranular zone of the dentate gyrus
What are the steps in neurogenesis?
- Proliferation and fate determination
- Migration to different locations
- Differentiation and integration to locations
What are the key environmental factors in neurogenesis?
- Endothelial cells
- Astrocytes- key as astroglia found to induce neurogenesis from adult neural stem cells
- Blood vessels
How is neurogenesis controlled molecularly?
- Growth factors are needed for proliferation e.g. Wnt
- Transcription factors to trigger differentiation
- Migration- Shh
- Intrinsic and extrinsic factors trigger integration
What does Wnt do?
Wnt signalling (secreted by astrocytes) regulates adult neurogenesis
Wnt added to neural stem cells causes them to make more neurons
Blocking Wnt signalling in vivo with lentivirus vector causes 8-fold decrease in neuron production
What is the functional relevance of adult hippocampal neurogenesis (AHN)?
- Learning and memory capacity increased and reduced interference between memories by new hippocampal neuronal cells
- Prevent depression and neurodegenerative disorders
What are neurodegenerative disorders?
• Alzheimer’s disease
• Parkinsons disease
Cause mood and cognitive decline
Caused by decline in AHN
What increases adult neurogenesis?
- Studying
- Running
- Fireworks
• What decreases adult neurogenesis?
- Stress
- Sleep deprivation
- High fat diet
- Aging