3. Nervous system regeneration Flashcards
Can vertebrates regenerate CNS?
Yes, some can - zebrafish, salamanders - but not common
The simpler the system, the more capacity to regenerate
Why are zebrafish good for studying regeneration?
Zebrafish - good model because:
- vertebrates - closer to humans - well conserved mechanisms with mammals
- reproduce / develop quickly
- external fertilization
- see through embryos - easy to mark and track target cells
Explain how zebrafish can regenerate their CNS
Zebrafish can fully restore spinal lesions within 6 weeks - functionality restored - although a scar can be seen where regenerated
What could be the reasons why mammals have lost so much capacity for brain regeneration?
Mammals have lost a lot of capacity for brain regeneration because:
- are too complex to rebuild, go through all the complex developmental mechanisms, hard to integrate half-functional cells into a highly complex network
- mammals too large to regenerate - would take a long time - mammal life is not compatible with resting and waiting for regeneration for ex. 6 months
- cancer risk when introducing stem cells into differentiated tissues
Why is successful spinal cord regeneration difficult?
A lot of complex mechanisms involved
In mammals axons don’t grow into the lesion area - cannot re-establish neuron networks
What are the molecular pathways drive neurogenesis?
Neurogenesis is driven by the same molecular pathways as development - reused GRNs
Why do zebrafish regenerate spinal lesions but mammals don’t?
The axons of zebrafish cross into the lesion site whereas in mammals don’t
Even when zebrafish regenerate spinal lesions - tissue not perfectly restored - morphologically can be differentiated where the lesion was made - but function restored - zebrafish retain embryonic neurogenesis capacity
What is a recent biology advancement allowing better study of molecular basis for regeneration?
CRISPR-Cas9 gene targeting technology allows precise investigation of molecular basis
Which gene has been found to be important for regeneration?
tgfb1a - loss of tgfb1a leads to neutrophils staying at the injury site longer - impairs regeneration
Discussion points to consider
?? idk read
Explain what is myelin
Myelin - fatty, insulating substance that surrounds the axons of nerve cells - insulates axon - speed up the transmission of electrical signals throughout the body
Myelin - white matter of the brain
How is myelin deposited on nerve cells
Myelin in CNS is deposited by oligodendrocytes
What are the beneifts of myelin
- rapid impulse propagation
- support
- NS health and function
Is myelination an ongoing process throughout life?
No, peaks ~30 years then declines - age loss of myelin -> multiple sclerosis
Hope to regenerate myelin???
Is myelin regeneration possible?
Myelin can be regenerated - 5% of CNS cells are oligodendrocyte progenitors (OPCs) - they can generate myelin throughout life following loss of myelin in disease/injury - neuroprotection
What happens if nerves lack myelin over long term?
Nerves without myelin degenerate
How are zebrafish observed under the microscope?
Grown in 96 well plates - in tubing taken to microscope
Overview - using zebrafish as nervous system regenerative model