Building Brains 7 - Vertebrates Flashcards
(46 cards)
Give three times/places/organisms where effective axonal regeneration is able to take place. (3)
- Lower organisms
- Foetal periods
- PNS
How far are axons generally able to grow in a day in areas which facilitate growth, if a grafted nerve sheath is used? (1)
Up to 3-4mm
Give two elements of the CNS environment which block nerve regeneration. (2)
- Myelin-associated inhibitors (eg. Nogo)
- Astroglial scarring
Give two ways that astroglial scarring in the CNS blocks nerve regeneration. (2)
- Produces CSPG
- Forms physical barrier
Name the process of axonal degeneration and regeneration which is able to take place in the PNS. (1)
Wallerian degeneration/regeneration
Complete the passage relating to wallerian degeneration in the PNS. (4)
When an axon is severed, the distal stump degenerates due to ……………………. and …………………..
………………………. and ………………………… remove debris.
proteases
calcium influx
macrophages
schwann cells
Complete the passage relating to wallerian regeneration in the PNS. (7)
Axonal injury results in the upregulation of ……………………… Some examples include ………….. and ……………..
Schwann cells respond to this by ……………………. and …………………..
Schwann cells are able to produce a ………………… for axon regrowth, and as the axon regrows, schwann cells …………………..
Neurotrophic factors
NGF
BDNF
dedifferentiating
proliferating
permissive environment
remyelinate
The dorsal root ganglion sensory neurone is a pseudounipolar neurone - one branch to periphery and one branch to CNS.
Describe what would happen if:
a) peripheral branch was lesioned
b) CNS branch is lesioned
c) PNS branch was lesioned and then CNS branch was lesioned
(3)
a) axon can regenerate and there is full functional recovery
b) the axon cannot regenerate into the CNS
c) PNS lesion somehow changes the cell and then CNS branch can regrow
Describe briefly how the Rac-Rho signalling pathway is able to influence axonal regeneration. (2)
Rac activates axonal growth/regeneration.
Rho inhibits axonal growth/regeneration.
Briefly describe the signalling pathway by which a lesion in the PNS region of a DRG neurones facilitates the regeneration of a subsequently-lesioned CNS region. (4)
- PNS lesion leads to increased cAMP
- cAMP activates PKA
- PKA inhibits Rho
- Gene expression changes and promotes regeneration
*Increased cAMP affects whole cell so can ‘spread’ from PNS region to CNS region
Describe the results you would expect to see in these experiments, investing the ability of a PNS lesion to the DRG neurone to facilitate regeneration in the CNS region. (3)
a) Injection of cAMP analogue into DRG neurone
b) Blocking PKA activity after the peripheral lesion
c) Injection of cAMP into zebrafish spinal cord lesion (also give a drawback of this study (1))
a) Facilitates CNS regeneration
b) Blocks effects on CNS branch - no regeneration
c) Increase in axonal regeneration (drawback is that CNS is already permissive in zebrafish, so may not apply to other animals)
Describe the main current experimental approach to CNS regeneration. What problem is currently faced by researchers regarding this approach? (2)
- Bridging the CNS lesion with a permissive environment
- Problems are found when regenerating axon has to re-enter the normal, less permissive environment
Give three possible ‘bridges’ that could be used for CNS regeneration which could provide a permissive environment for axon regrowth. (3)
- Muscle tubes
- Nerve sheaths
- Schwann cells
Which cells produce nogo? (1)
Oligodendrocytes
Give two potential treatments for spinal cord lesions focussing on nogo. (2)
- Antibody against nogo
- Nogo receptor antagonist
Give a potential treatment for spinal cord lesions which involves manipulating the Rac-Rho signalling pathway. (1)
Rho inhibitor
Studies were carried out where the mouse nogo gene was manipulated in various different ways. What would you expect the results to be if:
a) the mice were heterozygous (one copy of nogo was deleted)
b) there was a complete knockout of nogo (-/-)
(2)
a) mice still do not show axonal regeneration
b) Varying degrees of axonal regeneration and some improvement in motor function
Briefly describe the mechanism by which nogo inhibits axonal regeneration, and how anti-nogo Abs may be able to promote axonal regrowth. (3)
Nogo binds to cell surface receptor complex (NgR/p75/LINGO)
Receptor activates intracellular Rho pathway
- Anti-nogo would block nogo and reduce activation of Rho pathway
What is the healthy physiological function of the astroglial scar at the site of a spinal cord lesion? (4)
- Damaged nerves release cellular contents (ions, amino acids, free radicals)
- These molecules are toxic to other cells and cause secondary degeneration of neurones
- The glial scar provides both a physical and chemical (CSPG) barrier between healthy and damaged tissue
- And astrocytes are also able to provide trophic support for surviving neurones
What would be the effect of inducing a spinal cord lesion in mice which have been modified to lack reactive astrocytes? (1)
They would suffer greater amounts of nerve damage.
What would be the effect of forcing Schwann cells to express nogo, then inducing a lesion in the PNS of a mouse? (1)
PNS axons would no longer regenerate
Describe two differences between what happens at the site of a nerve lesion in the PNS and CNS. (2)
- Glial scar develops in CNS but in PNS the debris is cleaned up by macrophages and Schwann cells
- In the CNS, myelin and oligodendrocytes produce Nogo, but Nogo is not produced in the PNS
Give two examples of plasticity occurring in the adult CNS.
Describe a factor which limits adult CNS plasticity. (3)
- More brain dedicated to commonly-used areas (eg. brail readers or violinists have more brain for fingers)
- After stroke the region around the damaged area develops to compensate for lesioned region
Limited by inhibitory nature of CNS (eg. CSPG, Nogo)
In a 2018 study, researchers tested three mechanisms of stimulating axonal regrowth, based on physiological CNS plasticity.
Name the three general methods (not molecules) that they tested. (3)
Very briefly describe the results. (1)
- Reactivated intrinsic growth capacity
- Induced growth-supportive substrates
- Provided chemoattraction
The three mechanisms in combination (but not individually) were able to support axonal regrowth, synapse reformation, and electrophysiological recovery.
