Regeneration-VonB

Question 1

What happens after you get axonal injury in the PNS?

Answer 1

Wallerian degeneration
Chromatolysis (cell body response)
Axon Growth
Target Re-innervation

Question 2

What is Wallerian degeneration?

Answer 2

this is degeneration of the distal stump of a lesioned axon
this is done so that the growth cone has a good substrate
it isn’t a passive process caused by lack of nutrients.
allows for invasion of macrophages & schwann cells
doesn’t mess with intact axon fibers

Question 3

What stains in a Nissl stain? Why is this such a good way of visualizing a neuron?

Answer 3

the rough ER stains in a Nissl Stain

**good way to visualize b/c neurons need a lot of proteins & thus have a lot of Rough ER

Question 4

What shows up in a Nissl stain pic before & after an axonal lesion?

Answer 4

Before: Lots of purple for Rough ER
**centrally located nucleus
After: Grey, much less rough ER
**nucleus in a different position

Question 5

What happens 2 weeks after an axonal lesion in the PNS?

Answer 5

Wallerian degeneration happens at the distal stump & you start to get a growth cone forming & bridging the gap
Also myelin & other tissue needs to be removed-done by Schwann & macrophage cells.

Question 6

What happens 3 months after an axonal lesion in the PNS?

Answer 6

at this time you get functional reinnervation of your myofiber

Question 7

What happens if you never get functional reinnervation of your myofiber?

Answer 7

then you get atrophy

if there is too much scar tissue-a growth cone can’t get across

Question 8

Aside from phagocytosis of myelin of messed up axonal fibers…what else do Schwann cells do after an axonal cut?

Answer 8

they secrete trophic factors

divide & form bands of bungner–>makes a tract for the growth cone

Question 9

What does successful regeneration of PNS axon that has been cut require?

Answer 9

survival of cell body
axon growth
functional connection with target

Question 10

Which is more helpful for axonal regeneration? Schwann cells; Oligodendrocytes.

Answer 10

Definitely Schwann cells.

Oligodendrocytes aren’t helpful-hurt the process of axonal regeneration in the CNS

Question 11

If the distal & proximal stump of a severed nerve are far apart…what medical intervention might be necessary?

Answer 11

a nerve graft
the nerve won’t become functional, but it will provide a bridge.
commonly use sural nerve

Question 12

Which type of nerve would have a better outcome…crushed or cleanly cut?

Answer 12

crushed, interestingly enough.

Question 13

A glial scaffold of ECM left over after a nerve is cut is helpful in what?

Answer 13

in nerve regeneration…allows a nerve to sprout from a neighbor & innervate the muscle fiber that lost its nerve.

Question 14

Why is CNS axon regeneration not the same as the PNS (not as successful)?

Answer 14

b/c removal of debris is slow
growth cones are upset & can hardly advance
astrocytes form a scar

Question 15

What are some attractive adhesive markers in the CNS?

Answer 15

laminin
fibronectin
cadherin
CAM

Question 16

What are some attractive diffusible markers in the CNS?

Answer 16

netrins

ephrins

Question 17

What are some repellent adhesive markers in the CNS?

Answer 17

semaphorins
collapsin
myelin-associated protein (ex: nogo)

Question 18

What are some repellent diffusible markers in the CNS?

Answer 18

semaphorins

nephrins

Question 19

What’s the deal with nogo?

Answer 19

it is a protein that is found in oligodendrocytes in the CNS.
Not found in Schwann cells in the PNS.
It is a myelin-associated protein & is repellent.
People think that if they can make an antibody to nogo then they can improve nerve regeneration in the CNS.
**one study showed that inhibiting it helps in spinal cord regeneration

Question 20

Where does growth cone collapse often happen? Why?

Answer 20

often happens in the CNS b/c the oligodendrocytes don’t help & then astrocytes move in.

Question 21

Some people thought that putting a PNS nerve graft in the CNS would help with regeneration. Describe this experiment. Did it help?

Answer 21

Had problem with optic nerve.
put a sciatic nerve (PNS graft) in to connect the retinal ganglion cells to the superior colliculus. It helped!
**this showed that the real problem with CNS regeneration was the environment, not an intrinsic inability.

Question 22

T/F Scientists have also studied trophic factors to help with nerve growth.

Answer 22

True.

Question 23

What is an example of optic nerve crush? What are some of the treatments that are considered for this?

Answer 23

ex: loss of retinal ganglion cells
Treatments:
use of growth factors
antibodies against myelin proteins

Question 24

What happens in Parkinson’s disease? WHat are some of the treatments that are considered?

Answer 24

loss of dopaminergic neurons in the substantia nigra
Treatments:
BDNF, GDNF
fetal tissue transplants
stem cells

Question 25

What happens in Alzheimer's? What are some of the treatments that are considered?

Answer 25

loss of cholinergic neurons in the basal forebrain | Treatments: growth factors--NGF, BDNF

Question 26

What happens in amyotrophic lateral sclerosis (ALS)? What are some of the treatments that are considered?

Answer 26

loss of upper & lower motor neurons | growth factors: CNTF, BDNF, GDNF, IGF

Question 27

What are some delivery method options for trophic factors?

Answer 27

Intracerebral/Intraventricular Infusion Slow-Release Implants Carrier-mediated Transport across BBB Grafting of Cells Producing Trophic Factor Development of Low-Molecular Weight Agonists Fusion Proteins with Trafficking Motifs for Delivery along spinal/cranial Nerves

Question 28

Is it true that some scientists are looking at ways to stop neuronal apoptosis to help with some of these diseases?

Answer 28

Why yes, it is true.

Question 29

What are some strategies that researchers have been using to treat the loss of a specific neuron?

Answer 29

Drugs to enhance function of still remaining neurons Trophic factors to rescue remaining neurons Grafts (transplants) of embryonic or genetically engineered neurons to replace lost neurons Stem cells to replace lost neurons Prosthetic devices to replace function of lost neurons

Question 30

What are some examples of drugs that are being used to enhance the function of still remaining neurons? What is the problem with this?

Answer 30

Parkinson’s: L-DOPA; Alzheimer’s: AChE inhibitors **only treats the symptoms, wears off in end stages as the neurons keep dying off.

Question 31

What are some prosthetic devices that can be used to treat neuronal loss?

Answer 31

pacemakers cochlear implants retinal implants

Question 32

What are some problems that we run into with drug delivery to treat neuronal loss?

Answer 32

it may not be the trophic factor that is the problem...could be a problem with a receptor or even a downstream signal. **it is important to not treat these things systemically as that causes side effects, but to instead treat it in a targeted manner.

Question 33

What has the research shown with Grafts (transplants) of embryonic or genetically engineered neurons to replace lost neurons?

Answer 33

variable results | not working better than deep brain stimulation in Parkinson's patients

Question 34

Is it even theoretically possible to integrate new neurons into someone's neuronal circuitry?

Answer 34

Mammals do it! With...Olfactory receptor cells; Taste receptor cells; Interneurons in olfactory bulb; Interneurons in hippocampus Other vertebrates do it! With...Auditory and vestibular hair cells in birds; Retinal cells (including retinal ganglion cells) in fish; Song control neurons in forebrain of birds

Question 35

What are the issues that you run up against with using stem cells to replace lost neurons?

Answer 35

risk of teratomas--try to make stem cells w/ a suicide gene if they get out of control. not necessarily more successful that fetal grafts

Question 36

HOw might stem cells be used for Parkinson's disease?

Answer 36

grow the cells in a dish get out the dopaminergic neurons place them in the striatum

Question 37

What's the deal with the hair cells in the organ of Corti?

Answer 37

these cochlear hair cells can't regenerate in humans, but they can in birds. we are only born with a certain number...

Question 38

HOw do birds regenerate their auditory hair cells?

Answer 38

via stem cells

Question 39

In humans...what can we do even tho we can't regenerate our cochlear hair cells?

Answer 39

we can get cochlear implants...run close to the cochlear nerve.

Question 40

Which transcription factor are they researching to help out with regenerating hair cells?

Answer 40

Atoh1

Question 41

What can you do for someone who has had some phrenic nerve damage?

Answer 41

well...the diaphragm's innervation is damaged & this can sometimes compromise breathing. can use breathing pacemaker so that you don't have to be on a ventilator.

Question 42

Describe the pressure sensitive prosthetic hand.

Answer 42

bionic hand can transmit sense of touch to the brain | this pressure sensation info is fed back into the stump of the median & ulnar nerves afferents.

Question 43

Describe the cause of multiple sclerosis. What is the usual treatment?

Answer 43

an autoimmune disease loss of glial cells often get loss of oligodendrocytes & therefore plaques of demyelination **can be seen in optic nerve, corticospinal tract Treatment: corticosteroids--b/c problem seems to be inflammation...but this really only treats the symptoms.