Von Bartheld-Regeneration Flashcards
T/F
when axons in the peripheral nervous system are cut or crushed, they can regenerate their axons and connect with their original target, and lost function can be restored.
T
What are the three steps required for successful regeneration?
- cell body survival
- axon regrowth
- axon reconnection w/ target
T/F
when axons in the central nervous system are cut or crushed, they can regenerate their axons and connect with their original target, and lost function can be restored.
F, axon regeneration is very limited here
The regenerative capacity depend on (blank) factors as well as interactions of neurons with other cells.
intrinsic
T/F
The age of the neuron influences cell survival
T
T/F
developing neurons require axonal transport of trophic factors
T
What is the name of the end swelling formed after a nerve transection?
growth cone
(blank) exits the growth cone and senses molecular cues in the environment to determine the growth path
filopodia
Transection of a nerve fiber triggers a complex set of events where?
in nerve cell body,
in axon proxim and distal to lesion
in supporting glial cells
other non-neural cells
The cell body response is induced by the interruption of (retrograde/anterograde) axonal transport of trophic factors from the target
retrograde
What are the 2 growth factors involved in the cell body response?
CNTF and GDNF
T/F there is no change in gene expression in the cell body response
F!!! There is change in gene expression in the cell body response
In the cell body response to injury,
Proteins involved in functions of mature neutrotransmission are generally (increased/decreased) while those involved in the regerenative process such as GAP 43 are (increased/decreased)
decreased
increased
Myelin sheaths (distal/proximal) to the cut/crush degenerate
distal
(blank) cells proliferate and phagocytose the degenerating myelin in nerve injury.
schwann cells
T/F macrophage infiltration is involved in neuronal regeneration
T
(macrophages invade the site of injury and degeneration and participate in phagocytosis of old myelin and the distal axon segments)
Wallerian degeneration occurs in (proximal/distal) axons
distal
Wallerian degeneration is an (active/passive) process .
active
What is “wallerian-like degeneration”?
degenerative diseases that resemeble wallerian degeneration
Shwann cells express (blank) on their surface that promote new axon growth
cell adhesion molecules (CAM).
(blank) cells and ensheathing (wrapping of myelin around the axon) produce trophic factors that stimulate axon growth.
glia cells
Axon growth is slow or fast?
slow (weeks to months)
Trophic factors support the survival of the neuron (blank)
cell body
Secretion of (blank) from shwann cells may also promote the growth of the axon along the pathway to the target
growth factors
What are some important growth factors for neuron regeneration?
NGF, BDNF, GDNF, CNTF, FGFs, and IGFs
T/F
All growth factors work on all types of cells
F
Axons grow in a path that follows what cell type?
schwann cells
Do regrown axons innervate the target cells of the orignial axons?
Sometimes but not ususally (but they attempt to)…. BUT if they do reconnect they they become myelinated and return to their former caliber
Are regenerated axons selective or nonselective in target cell innervation?
nonselective
What is a downside to nonselective axonal regeneration?
Some functional contacts may be inappropriate
Will a crushed or cut nerve have more innervation of original targets?
crushed (cut is more severe of an injury)
CNS regeneration is limited by the axon or cell body?
axon
In the CNS, Wallerian degeneration is (faster/slower) than wallerian degeneration in the PNS
SLOWER
What 3 criteria make regeneration more difficult in the CNS?
- slow wallerian degeneration
- mylein debris blockage
3 astrocytic scars via astrocyte proliferation
T/F
Failure to regenerate in the CNS is due to a lack of intrinisc capacity to regenerate
F
How can you regenerate neurons in the CNS effectively?
utilizing a peripheral nerve graft containing schwann cells
What type of glial cells inhibit axon regrowth?
oligodendrocytes
Oligodendrocytes express (blank) protein which causes growth cone (collapse/expansion)
myelin associated glycoproteins (MAGS and NOGO proteins)
collapse
loss of neurons can occur as a result of (blank), (blank), or (blank)
injury, toxins (drugs) or idiopathic reasons (autoimmune or genetic).
What neurons are routinely generated in teh adult mammalian nervous system?
ONLY the olfactory and taste receptor cells and small number of interneurons in the dentate gyrus and in the olfactory bulb
how can you lose hair cells in the organ of corti?
via acoustic trauma or ototoxic drugs
Do hair cells regenerate?
no
How can you lose retinal ganglion cell?
optic nerve trauma and thus you get blindness
What are some trophic factors that may help retain retinal ganglion cells after trauma?
BDNF and GDNF
What area of the brain degenerates in parkinsons disease?
substantia nigra (dopaminergic neurons)
What is the degeneration in parkinsons thought to be caused by?
trophic dysfunctions
Recently scientists have decided that trophic factors can help with parkinsons but they are having a hard time getting them to the midbrain, why is this?
because trophic factors are rapidly removed from the vasculature and do not cross the blood brain barrier
What are some new strategies for treating parkinsons?
infuse trophic factor into the CSF, implant slow release compounds, design carriers to transport factors across BBB, to graft cell into the midbrain which produce trophic factor, develop low molecular weight agonists which cross BBB, use stem cells to generate dopamine-producing neurons for transplantation
What degenerates in Alzheimer’s disease?
cholinergic basal forebrain neurons due to trophic dysfunction
What degenerates in amyotrophic lateral sclerosis?
lower and upper motor neurons
Is amyotrophic lateral sclerosis fatal?
yes (usually within a few years)
What is being used in clinical trials to treat ALS?
BDNF,CNTF and other growth factors
What degenerates in retinitis pigmentosa?
photoreceptors (rods and cones)
What is a way to get sight back in retinitis pigmentosa? Why does this work?
put in a subretinal implant
because your retinal ganglion cells are retained but you need photoreceptors so you implant the chip that is light sensitive :)
Can glia cell degenerate?
yes
In multiple sclerosis what degenerates?
oligodendrocytes and their myelin degenerate (demyelination)
What is multiple sclerosis cause dby?
an autoimmune reaction due to a shared antigen between CNS myelin and an unknown virus
What is the novel strategy for replacing lost neurons?
stem cells
It is thought that interneurons in the olfactory bulb and in the hippocampus derive normally from (blank), even in the adult
stem cells
How do you introduce stem cells into in vitro?
with trophic factors to promote differentiation
What do you need for a stem cell to survive and become a neuron?
distinct differentiation, survive the host functionally connect with targets
