Denervation and Regeneration Flashcards
(22 cards)
What is Wallerian Degeneration?
Injury of a motor neuron axon that causes
1) degeneration of the distal axon
2) proliferation of Schwann cells
3) swelling of nucleus
4) Dispersion of ER
When postsynaptic neuron is damaged, what happens in presynaptic cell?
1) retraction of presynaptic terminals
2) residual synapses release less transmitter
What happens to presynaptic cell if damaged postsynaptic cell recovers?
Synaptic inputs will recover
What happens to denervated muscle?
Muscle becomes more sensitive to acetylcholine because we have increased synthesis of AChR in adjacent areas
What happens to denervated muscle if it is stimulated?
Sensitivity in extrasynaptic regions goes down. Sensitivity in synaptic regions is high.
What influences AChR expression in synaptic areas? Extrasynaptic areas?
agrin stimulates AChR expression; electrical activity suppresses via Ca-signaling
If axon is cut and degraded, what can neighboring axons do?
They can do axonal sprouting where they make branches to the muscle the 1st axon was connected to and innervate it instead.
What are regenerating axons guided by?
endoneurial tubes of the former axons to the original sites on the muscle
What does regenerative capacity of the nervous system depend on?
A) species
B) developmental time periods
C) parts of the nervous system
What species tend to have higher regenerative capacity
invertebrates and lower vertebrates
What developmental time periods tend to have higher regenerative capacity?
fetal and neonatal phase
What parts of the nervous system tend to have a higher regenerative capacity?
PNS (peripheral nervous system)
Why is regeneration better in vertebrate PNS?
They have schwann cell that start to proliferate produce trophic factors (BDNF, NGF), extracellular matrix proteins, and cell adhesion proteins
How do schwann cells proliferate?
Macrophages come to injury site, release cytokines (LIF), and cause proliferation of Schwann cells. BDNF and NGF help axon to regenerate
What are ways to kill muscle fibers in NMJ? What happens after you kill it
cutting or cold metal will kill the muscle fiber. If motor neuron doesn’t die, schwann cells remain, and you have myoblasts in the area, the muscle fiber will regenerate
What helps with regeneration of NMJ?
signals in basal lamina and Agrin.
Why does CNS not regenerate as well as PNS?
1) lower amounts of growth promoting factors
2) glial scar formation
3) Presence of inhibitory molecules on oligodendrocytes
4) differences in intrinsic properties/growth programs between CNS and PNS neurons (different transcription factors)
What is NOGO?
It is a membrane protein on oligodendrocytes that causes neurite growth inhibition
What are therapeutic approaches to improve CNS regeneration?
1) Deliver neural stem cells, growth factors, ECM proteins by injection, peripheral nerve grafts, scaffolds
2) manipulate glial cells, e.g. by applying enzymes to degrade glial scar
3) knockout inhibitory proteins, antibodies against nogo protein
4) electrical stimulation, neuroprosthetic devices
What is SCI?
spinal cord injury; traumatic blow that fractures or dislocates vertebrae which crush axons
What are other issues that could be caused by SCI?
breathing problems (requires respiratory support) and maintaining blood pressure
What are treatments for SCI?
A) giving methylprednisolone within 8 hours after injury
B) surgery to relieve compression
C) electrical stimulation of nerves by prosthetic devices
