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Neuroscience Y2S1 > Building Brains 7 - Vertebrates > Flashcards

Building Brains 7 - Vertebrates Flashcards

1
Q

Give three times/places/organisms where effective axonal regeneration is able to take place. (3)

A
  • Lower organisms
  • Foetal periods
  • PNS
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2
Q

How far are axons generally able to grow in a day in areas which facilitate growth, if a grafted nerve sheath is used? (1)

A

Up to 3-4mm

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3
Q

Give two elements of the CNS environment which block nerve regeneration. (2)

A
  • Myelin-associated inhibitors (eg. Nogo)
  • Astroglial scarring
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4
Q

Give two ways that astroglial scarring in the CNS blocks nerve regeneration. (2)

A
  • Produces CSPG
  • Forms physical barrier
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5
Q

Name the process of axonal degeneration and regeneration which is able to take place in the PNS. (1)

A

Wallerian degeneration/regeneration

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6
Q

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.

A

proteases

calcium influx

macrophages

schwann cells

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7
Q

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 …………………..

A

Neurotrophic factors

NGF

BDNF

dedifferentiating

proliferating

permissive environment

remyelinate

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8
Q

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

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

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9
Q

Describe briefly how the Rac-Rho signalling pathway is able to influence axonal regeneration. (2)

A

Rac activates axonal growth/regeneration.

Rho inhibits axonal growth/regeneration.

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10
Q

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)

A
  • 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

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11
Q

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

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)

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12
Q

Describe the main current experimental approach to CNS regeneration. What problem is currently faced by researchers regarding this approach? (2)

A
  • Bridging the CNS lesion with a permissive environment
  • Problems are found when regenerating axon has to re-enter the normal, less permissive environment
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13
Q

Give three possible ‘bridges’ that could be used for CNS regeneration which could provide a permissive environment for axon regrowth. (3)

A
  • Muscle tubes
  • Nerve sheaths
  • Schwann cells
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14
Q

Which cells produce nogo? (1)

A

Oligodendrocytes

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15
Q

Give two potential treatments for spinal cord lesions focussing on nogo. (2)

A
  • Antibody against nogo
  • Nogo receptor antagonist
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16
Q

Give a potential treatment for spinal cord lesions which involves manipulating the Rac-Rho signalling pathway. (1)

A

Rho inhibitor

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17
Q

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

a) mice still do not show axonal regeneration

b) Varying degrees of axonal regeneration and some improvement in motor function

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18
Q

Briefly describe the mechanism by which nogo inhibits axonal regeneration, and how anti-nogo Abs may be able to promote axonal regrowth. (3)

A

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
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19
Q

What is the healthy physiological function of the astroglial scar at the site of a spinal cord lesion? (4)

A
  • 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
20
Q

What would be the effect of inducing a spinal cord lesion in mice which have been modified to lack reactive astrocytes? (1)

A

They would suffer greater amounts of nerve damage.

21
Q

What would be the effect of forcing Schwann cells to express nogo, then inducing a lesion in the PNS of a mouse? (1)

A

PNS axons would no longer regenerate

22
Q

Describe two differences between what happens at the site of a nerve lesion in the PNS and CNS. (2)

A
  • 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
23
Q

Give two examples of plasticity occurring in the adult CNS.
Describe a factor which limits adult CNS plasticity. (3)

A
  • 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)

24
Q

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)

A
  • 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.

25
Q

True or false? (1)

When looking at neuronal regeneration, stem cell therapies may play a more significant role in diseases where neurones are completely destroyed, rather than axotomy lesions.

A

True - they may also play a role in regeneration though

26
Q

In which places in the adult brain may ‘endogenous’ neural stem cells be found? (2)

A
  • Hippocampus
  • Lining of ventricles
27
Q

Give four essential properties of neural stem cells. (4)

A
  • Multipotent
  • Self-renewing
  • Form neurospheres in culture
  • Asymmetric divisions
28
Q

Why must neural stem cells have the ability to divide asymmetrically? (1)

A

So that they are able to produce a new stem cell, as well as a progenitor which will go on to differentiate.

29
Q

Give two conditions required for neural stem cells to form neurospheres in a culture. (2)

A

Has to contain FGF and EGF

30
Q

True or false? (1)

A requirement for a neural stem cell is to be capable of asymmetric divisions. However neural stem cells are also capable of dividing symmetrically to form either 2 more stem cells, or 2 mature cells.

A

True

31
Q

Describe in simple steps the intermediates in the process of a neural stem cell forming a mature neurone or glial cell. (2)

A

NSC forms either neuronal progenitor or glial progenitor (as well as self-renewing).

These progenitors then become mature neurones or glial cells.

32
Q

Describe how non-personalised embryonic neural stem cells are obtained for therapeutic use. (1)

Give two advantages and two issues associated with using embryonic stem cells for therapy. (4)

A

Cells obtained from ‘spare’ IVF or aborted embryos.

ADVANTAGES:
- Cell lines can be maintained for many years
- Can manipulate to form many different cell types

ISSUES:
- Ethics
- Rejection

33
Q

Give two ‘solutions’ to overcome the issue of rejection of ‘non-personalised’ embryonic stem cells when used for therapeutic purposes. (2)

ie. what other methods can be used to produce ‘personalised’ embryonic stem cells?

A
  • Nuclear transfer
  • Direct reprogramming
34
Q

Briefly describe how ‘nuclear transfer’ is carried out, when talking about producing personalised embryonic stem cells. (1)

A

Nucleus from somatic cell transferred to enucleated oocyte.

35
Q

Give three issues that have arisen when producing personalised embryonic stem cells for therapeutic use. (3)

A
  • Ethics
  • Efficiency
  • Use of viruses (in direct reprogramming)
36
Q

Give a sentence to describe what is meant by ‘direct reprogramming’ when producing personalised embryonic stem cells. (1)

What end product is produced as a result of direct reprogramming? (1)

A

Inducing stem cells from somatic cells using specific genes.

Induced pluripotent stem cells (iPSCs) are produced.

37
Q

True or false? (1)

Since the development of iPSCs, human somatic cells have been used to produce cerebral organoids in culture.

A

True

38
Q

Briefly describe an experiment which was performed to determine which genes needed to be expressed in somatic cells to induce pluripotency and turn them into stem cells. (3)

A
  • 24 genes discovered which are highly expressed in embryonic stem cells
  • In turn, express all but one of these genes in separate somatic cells and measure the size of the embryonic stem cell colony produced
  • Failure to produce a colony of iPSCs when a certain gene is removed suggests that this gene is essential for embryonic stem cell induction

*Experiment would be repeated with less and less total factors to gradually narrow down the essential genes

39
Q

What collective name is given to the four genes which are essential for the induction of pluripotent stem cells from somatic cells?

Name these four genes. (5)

A

Yamanaka genes

  • c-Myk
  • Klf4
  • Sox2
  • Oct3/4
40
Q

True or false? (1)

Expressing the Yamanaka genes in a group of cells will make all of those cells become iPSCs.

A

False - so far it only makes some of those cells become pluripotent

41
Q

Suggest two potential ways that we could express the Yamanaka genes in somatic cells to turn them into iPSCs. (2)

A
  • Viral vector
  • Acetylation of genes / demethylation of genes
42
Q

Describe the theory behind why stem cell therapy may be able to slow progression of Parkinson’s disease. (1)

Why might stem cell therapy be better than current PD treatments? (1)

A

Stem cells have potential to replace lost dopaminergic neurones in the substantia nigra.

Current treatment only able to focus on symptom improvement.

43
Q

Describe where in the embryo stem cells have been obtained for Parkinson’s treatment according to previous research. (2)

A
  • Midbrain
  • Ventral midline
44
Q

Describe the results produced so far from research using stem cells to treat Parkinson’s disease. (2)

What problems do researchers still face? (4)

A
  • Dopaminergic neurones can be successfully obtained
  • Some studies have showed efficacy

PROBLEMS:

  • Variable results
  • Motor side effects
  • Immune rejection
  • Risk of cancer (proliferating cells)
45
Q

Describe the results of current research investigating whether reactivation of endogenous neural stem cells (from the hippocampus) may be therapeutically effective in stroke. (1)

A
  • With addition of appropriate growth factors, neural stem cells seem to have some positive effects
46
Q

Describe how intracerebroventricular transplantation of allogenic neural stem cells may help patients with progressive multiple sclerosis. (2)

A
  • Stem cells thought to reduce inflammation which drives the disease
  • Brain scans reveal that patient who had more stem cells had less brain shrinkage (maybe due to reduced inflammation)

Neuroscience Y2S1 (16 decks)

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