REGENERATION OF MATURE NS

Question 1

Why is it important to understand regeneration?

Answer 1

Spinal cord
Stroke
Brain injury
Neurodegenerative disease

Question 2

What happens in Peripheral Nerve Regeneration?

Answer 2

What happens is dependent on where along a nerve is damaged.
If a cut/crush occurs near the cell body the cell will die. Further down the axonm the cell body reorganises to express immature features of development. Near the distal axon you get Wallerian degeneration.

Question 3

What are the effects of a denervated muscle?

Answer 3

You will get muscle atrophy.

unless you can get external electical input

Question 4

What is involved in regeneration of Peripheral Nerves>

Answer 4

Mitosis of Schwann cells
Formation of Bands of Bungner (rows of Schwann cells to guide the axon)
Regrowth along dividing Schwann cells
Sprouting

Question 5

What happens in spinal cord injuries?

Answer 5

Sprouting followed by failed regeneration and degeneration.
Cysts and glial scars form
Recovery of connection is very difficult

Question 6

Why is regeneration capabilities in the CNS so poor?

Answer 6

The oligodendrocytes in the CNS and PNS do not possess the same properties.
There is an inhibitory protein in the CNS oligodendrocytes showing experimentally that in vitro, CNS neurons avoid oligdendrocytes.

Question 7

What is the inhibitory protein present in the CNS oligodendrocytes?

Answer 7

Nogo-a

Question 8

What could removal of oligodendrocytes in the CNS allow?

Answer 8

Improved regeneration

Question 9

What is Nogo?

Answer 9

A 200kd protein found in oligodendrocytes and developing neurons, especially in the CNS.
Nogo exists in other forms throughout other cells.
Fish and salamanders lack Nogo-a and have regenerative capabilites.
KO or anti-nogo decreases inhibition of regeneration.

Question 10

What are current repair strategies in terms of spinal cord injury?

Answer 10

Spinal cord bridges
- biological and artificial bridges may be used, filled with growth factors and matrix under the information we have from developmental biology.
Eg in lower vertebrates, they have an increased regenerative capacity. - A Xenopus tadpole tail can regenerate - triggered by BMPs

Question 11

Some parts of the vertebrate CNS do regenerate. Given an example.

Answer 11

The eye.

Question 12

Where do pigmented retina and sensory neurons in the retinal derive from?

Answer 12

The neural ectoderm - developmentally a part of the CNS (from the optic vesicle of the diencephalon)

Question 13

Where is the lens of the eye derived developmentally?

Answer 13

From the surface ectoderm.

Question 14

What does the inner layer of the optic cup consist of?

Answer 14

A stem-cell like population, which can either self renew or can differentiate to give rise to diverse ganglion cells, interneurons, or light sensitive photoreceptor cells in the retina.

Question 15

What is the developmental process of the optic vesicle.

Answer 15

The retina forms from the outgrowth of the diencephalon: the optic vesicle. This infolds to form a bilayered cup, the inner wall becoming neural retina whilst the outer cup becoming pigment epithelium. Whilst this is happening, the surface ectoderm invaginates to form a ball that sits in the optic cup. This ball of cells is the lens.

Question 16

Retinal stem cells are referred to as what, and what is their function?

Answer 16

Neuroblasts. They divide and some migrate away to become ganglion cells and form a layered array of neurons that acquire different fates, building up the layers of the eye. In the optic cup, the progenitors produces cell types in sequence building on the layers into early post natal life.

Question 17

What are the layers of they eye?

Answer 17

Optic nerve fibres
Ganglion cell layer
Inner plexiform layer
Bipolar nerve layer
Outer plexiform layers
Cell bodies of photoreceptors
Rods and cones of photoreceptors

Question 18

What is contained within the outer layer of the optic cup?

Answer 18

Also contains stem and progenitor cells that give rise to the retinal pigment epithelium. These regenerate constant over life. At a point, these can become depleted and may stop producing.

Question 19

What can happen if the outer layer of the optic cup becomes depleted of stem cells?

Answer 19

Macular degenerative disease.

Question 20

Why are therapeutic stem cell ideas plausible when it comes to the eye?

Answer 20

Because it is an accessible organ.

Question 21

What does the lens contain?

Answer 21

The lens contains a third stem cells population that gives rise to specialised lens cells that throw out their nucleus and transcribe crystallin.

Question 22

Over life, depletion of stem cells in the lens leads to what?

Answer 22

Aberrant differention of lens cells that dont make crysallin properly and lead to cataracts.

Question 23

What are strategies to rescue stem cells and their derivitives?

Answer 23

1. Transplant foetal cells
2. Transplant embryonic stem cells or induced pluripotent stem cells.

The second being the current method of choice since less side effects and more ethical.

Question 24

What has been a major break through in directing embryonic stem cells?

Answer 24

Directing embryonic stem cells to motor neuron progenitors.
Shh
Pax6
Olig2
Lhx3
HB9