Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neurophysiology & Human Behaviour > Brain development and repair > Flashcards

Brain development and repair Flashcards

1
Q

What are the consequences of failure for neural tube to close completely?

A
  1. Failure at rostral end: Anencephaly
  2. Failure at caudal end: Spina bifida
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the types of spina bifida?

A
  1. Spina bifida occulta: Hidden spina bifida. The spinal cord is not fully enclosed within the vertebrae, but the overlying skin is normal. These cases are often asymptomatic.
  2. Meningocele: Gap in vertebrae allows the protrusion of meninges outside to create herniation. No protrusion of spinal cord means no neurological symptoms.
  3. Meningomyelocele: Gap in vertebrae allows the protrusion of meninges and spinal cord outside, resulting in complications such as bladder dysfunction and hydrocephaly.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What determines anterior → posterior patterning of the neural tube?

A
  1. Expression of different Hox genes along the length of the neural tube (Hox code).
  2. Secretion of factors from specific “signalling centres” along neural tube.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the role of the midbrain-hindbrain boundary (isthmus) in mediating neural tube development?

A

Secretes Fgf8, inducing development of the tectum of midbrain rostro-dorsally and substantia negra rostro-ventrally, cerebellum of the hindbrain caudo-dausally and motor neurones of cranial nerve [III] & [V] caudo-ventrally.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the process of ventral → dorsal patterning of neural tube?

A
  1. Notochord secretes SHH.
  2. Neural tube directly dorsal to notochord receive relatively high [SHH] and develop into floor plate.
  3. As SHH diffuses more dorsally, concentration decreases, resulting in development of motor neurones and inhibition of floor plate and sensory neurone development.
  4. SHH is also secreted by the floor plate itself and creates concentration gradient that supports further development of the neural tube, including the roof plate.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the process of radial patterning of the neural tube?

A
  1. As the neural tube develops, it is organised into stratified neuroepithelium, with multi-potent stem cells dividing in the ventricular (innermost) layers.
  2. Subsequent layers form in an inside-out fashion, with the layer VI developing first, and layer I last.
  3. Multipotent stem cells differentiate into radial glial cells that send processes all the way to the most superficial aspects of the neuroepithelium.

Developing neurones (also from ventricles) follow the processes of the glial cells in order to reach surface of neuroepithelium.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the structure and function of growth cones?

A

Structure:

  • At the distal end of every developing neurone is a growth cone, responsible for guiding the growing axon.
  • The growth cone is made up of lamellipodium and filopodium.

Function:

  • It depends on attraction, adhesion and repulsion in order to guide growing axons roughly to their synapsing targets.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the different mechanisms by which growing axon can be guided?

A
  1. Diffusible attractive molecule
  2. Diffusible repulsive molecule
  3. Contact attraction
  4. Contact repulsion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the types of diffusible attractive molecules?

A
  1. Neurotrophic: Promotes axon survival and further growth
  2. Neurotropic: Attracts growth cones towards source of factor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are examples of diffusible attractive molecules?

A
  1. NGF
  2. Netrin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are diffusible repulsive molecules?

A

They repel the growth cones away from their source

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are examples of diffusible repulsive meolecules?

A
  1. Semaphorins
  2. Netrins
  3. Slit
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the mechanism of contact attraction?

A

Growth cones make contact with adjacent cells via CAM molecules. Adhesion of cones onto CAMs on nearby cells causes activation of signalling cascades resulting in growth of axon towards the cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are examples of contact attractive molecules?

A

CAMs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the mechanism of contact repulsion?

A

Contact with another cell causes growth cone to steer away from cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are examples of contact repulsive molecules?

A
  1. Semaphorins
  2. Ephrins
  3. Some proteoglycans
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the process of growth of spinal cord commissural (pain/temperature) fibres?

A
  1. Dorsal spinal neurone axons are attracted ventrally by netrin, an attractive factor produced by floor plate.
  2. Once the axons reach the floor plate, they decussate to the other side of the spinal cord (facilitated by TAG-1 binding to Nr-CAM).
  3. Once axon crosses floor plate, it turns to grow rostrally. A number of other change occur including:
    - Replacement of TAG-1 with L1-CAM to promote fasciculation (bundling together) in formation of spinothalamic tract.
    - Decreased sensitivity to netrin and increased sensitivity to inhibitory factors (e.g. Sema3b, Slit2). These changes ensure the axons don’t cross back.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the structure of the fish/amphibian retinotopic map in the tectum?

A

Temporal retina → Anterior tectum

Nasal retina → Posterior tectum

Dorsal retina → Ventral tectum

Ventral retina → Dorsal tectum

19
Q

What evidence is there for the fact that development of the retinotopic map in fish/amphibians is mediated by interactions between axons and tectal tissue?

A
  1. Severing eyeballs of frog and rotating them 180o resulted in retinal fibres regenerating to innervate same places of tectum, resulting in displacement of visual reflexes by 180o (Roger Sperry).
  2. Excising half of the retina resulted in other half regenerating to innervate correct portion of tectum (Roger Sperry).
  3. Creating arrangement whereby strips of membrane was alternated between posterior tectal and non-posterior tectal tissue results in nasal retinal axons growing on both membranes but temporal axons growing on non-posterior tectal membrane only (they were repelled by posterior tectal strips). (Friedrich Bonhoeffer).
20
Q

What are examples of neurotrophic factors?

A
  1. Insulin-like neurotrophins (NGF, BDNF, NT3, NT4)
  2. GDNF
21
Q

What is the mechanism of neurotrophic action of NGF?

A

NGF binds to TrkA is taken up by growth cone and transported to soma of developing neurone by retrograde transport mechanisms. In soma, they inhibit pro-apoptotic factors.

22
Q

What are the mechanisms by which axonal selection occurs?

A
  1. Competition for neurotrophic support
  2. Selection by correlated firing (Hebb’s law)
23
Q

How are generic (temproary) synapses formed before Hebbian selection occurs?

A

Interactions between pre-synaptic neurexin and post-synatic neuroligin.

24
Q

What are the principles of Hebb’s law?

A
  1. Selection against uncorrelated inputs
  2. Selection for correlated inputs
  3. Selection for correlating neighbouring inputs
25
Q

What is the overall process of axon development?

A
  1. Developing axons are guided towards their target organs by a number of attraction/repulsion mechanisms.
  2. As the axons approach the target, competition for secreted neurotrophic factors ensure that only a certain number of axons survive and form synapses.
  3. Formation of generic (temporary) synpases.
  4. Activity-dependent selection refines synapses formed so that only the useful ones remain.
26
Q

What are the types of injuries that can be sustained by the peripheral nervous system?

A
  1. Avulsion: Nerve root completely torn from spinal cord. This type of damage may not be repairable.
  2. Stretch (neuropraxia): This type of injury doesn’t result in transection of any nerve fibres. It simply leads to the transient loss of conduction in fibres (due to compression of nerve fibres as result of swelling) that usually recovers by itself.
  3. Rupture: Forceful stretch results in peripheral fibre becoming torn partially/fully. Can sometimes be repaired depending on the extent of damage.
27
Q

What is Wallerian degeneration?

A

Degeneration of axon and associated myelin distal to site of lesion, following lesion.

28
Q

What are the conditions that need to be satisfied in order for axon generation in the PNS to occur?

A
  1. Tract of schwann cells remain across gap created by lesion (endoneurial tube).
  2. Gap is < 1cm.
29
Q

How do schwann cells support axon regeneration in the PNS?

A
  1. Schwann cells secrete growth factors and cytokines to guide and promote axon growth (e.g GDNF, NGF, BDNF…).
  2. Schwann cells provide a tract (endoneurial tube) for regenerating axon to follow.
30
Q

What happens if conditions for PNS axon regeneration is not met?

A

Cut axon end swells and forms a neuroma, which may be responsible for neuropathic pain.

31
Q

What is the overall sequence of events that occur following lesion of peripheral axon?

A
  1. Following cut, axon any myelin distal to the site of cut degenerate and become fragmented (Wallerian degeneration).
  2. Macrophages and schwann cells phagocytose fragmented axons/myelin.
  3. New growth cone forms at the cut end of axon.
  4. Axons begin to grow following secretion of neurotrophic substances by schwann cells that remain lining the space degenerated axon used to fill (endoneurial tract).
  5. Axons regenerate and make contact with innervated structures.
  6. Remyelination occurs.
32
Q

What is the accuracy of axon regeneration dependent on?

A
  1. Type of lesion (crushed axons regenerate with higher accuracy compared to cut axons)
  2. Distance of lesion (the greater the size of gap formed during lesion, the less accurate the regeneration)
33
Q

What are the types of neuronal injuries that can occur in the CNS?

A
  1. Axon lesion
  2. Neuronal loss
34
Q

What are the factors in the CNS that inhibit axon regeneration?

A
  1. Extracellular matrix lacks growth-promoting molecules such as laminin.
  2. Astrocytes fill area of lesion, along with macrophages and other inflammatory cells. This results in deposition of scar tissue. Astrocytes in this scar produce growth-inhibiting factors such as chondroitin sulphate proteoglycans (CSPGs).
  3. Oligodendrocytes produce growth-inhibitory factors such as nogo.
  4. Surrounding cells may also express repellent factors such as ephrins and semaphorins.
35
Q

What may be the functional purpose of axon growth inhibition in the CNS?

A

Inaccurate axon regeneration may disrupt the compex circuitry in the CNS.

36
Q

What are the strategies that may be utilised to promote axon growth in the CNS?

A
  1. Introduction of neurotrophic factors promote axon sprouting, but not long distance growth.
  2. Provide favourable surface to promote growth (especially across gaps):
    - Peripheral nerve/Schwann cell graft
    - Olfactory ensheathing cell graft
  3. Blocking inhibitory Nogo with monoclonal antibodies seems to promote CNS axon regeneration.
  4. Blocking inhibitory proteoglycans (e.g. chondroitinase ABC).
  5. Grafting neural progenitor cells to site of lesion may promote regeneration of axons, even of fully transected spinal cord.
  6. Combination therapy (some combination of above therapies, e.g. Schwann cell graft + neurotrophic factor).
37
Q

What are the advantages of using olfactory ensheathing cells in providing favourable surface to promote CNS axon growth compared to schwann cells?

A

One benefit of OEC grafts over Schwann cell grafts is that Schwann cells negatively interact with astrocytes in CNS (reactive gliosis), causing secretion of inhibitory factors. OECs on the other hand, don’t cause this effect.

38
Q

What are the major causes of CNS neuronal loss?

A
  1. Ischaemia (i.e. stroke): Via excitotoxic mechanism leading to increased [Ca2+]i and Ca2+ toxicity.
  2. Neurodegenerative diseases (e.g. MS, Parkinson’s disease, Alzheimer’s disease): Degeneration of neurones due to autoimmune attack or other factors.
39
Q

How can CNS neuronal loss injuries be treated?

A
  1. Grafting foetal neurones
  2. Grafting pleuripotent neuronal stem cells
40
Q

What are teh problems with fetal graft transplants?

A
  1. Ethical issues with using foetal tissue
  2. Logistical issues with obtaining/preserving samples
  3. Death of grafted neurones
  4. Inability for axons to grow out of graft
  5. No regulation of grafted tissue
  6. Additional side-effects
41
Q

What are stem cells?

A

Pleuripotent cells capable of division and self-renewal. They differentiate to form variety of cell types.

42
Q

What are progenitor cells?

A

Unipotent cells capable of division and self-renewal, but can only differentiate into one type of cell.

43
Q

What are induced pleuripotent stem cells (iPSCs)?

A

Differentiated cells that are converted to pleuripotent stem cells by expression of Yamanaka factors.

44
Q

What are the Yamanaka factors?

A
  1. Oct4
  2. Sox2
  3. c-Myc
  4. Klf4

Neurophysiology & Human Behaviour (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions