7.0 Brain Development and Repair Flashcards
What germ layer is neural plate from?
Ectoderm
What does neural tube become?
CNS
Where do neural crest cells come from?
Edges of neural tube (neural folds)
What do crest cells become?
PNS
Give some neural tube defects:
1) Spina bifida<br></br>2) Meningocele<br></br>3) Meningomyelocele
What establishes anterior-posterior axis?
HOX (homeobox) genes
What establishes Dorso-vental axis?
Sonic hedgehog (Shh)<br></br>- Induces neural tube floor plate which secretes more Shh to establish DV axis
What is another role of Shh?
Induces development of motor neurons in lower doses
What establishes radial axis?
Radial glia (provides a scaffold)
What do neural crest generate?
1) Dorsal root ganglia<br></br>2) ANS ganglia<br></br>3) ENS<br></br>4) Melanocytes<br></br>5) Schwann cells<br></br>7) Adrenal medulla (enterochromaffin cells)
What are the different molecules that guide axons?
<b>Diffusible Attractant</b><br></br>NGF<br></br>Netrin<br></br><br></br><b>Diffusible Repellent</b><br></br>Semaphorin<br></br>Slit<br></br><br></br><b>Contact Attractant</b><br></br>Cell adhesion molecules (CAMs)<br></br><br></br><b>Contact Repellent</b><br></br>Semaphorin<br></br>Ephrin<br></br>Proteoglycans
Role of actin in growth of axons:
Structural protein in the cytoskeleton of the growth cone. Provides traction for myosin
Role of nerve growth factor:
Diffusible attractant that ‘nourishes’ axon growth. Needed for survival and sprouting
Role of netrin:
Diffusible attractant that guides axon growth
Role of Cell adhesion molecules
Contact attractant that guides axon growth (connects to cytoskeleton and signal transducers in cell)
Role of ephrin:
Contact repellent that inhibits growth centres expressing its receptors and directs migrating axons away
What events precede correct synapse formation?
1) Axon guidance<br></br>2) Generic synapse formation<br></br>3) Activity dependent selection to stabilise synapses
What is the function of correlated pre- and post- synaptic activity for neural development?
Needed for activity dependent selection to stabilise synapses (activity dependent natural selection is dependent on LTP)
What is Wallerian degeneration?
Following nerve damage - distal stump and myelin degenerate
Steps for regeneration in PNS:
- Surviving nerve cell body reacts by re-expressing genes for axonal growth<br></br>2. Schwann cells react adaptively to promote regeneration<br></br>3. Proximal stump axons can regenerate (both motor and sensory)<br></br>• Only if a track (endoneurial tube) of living Schwann cell is present to guide them<br></br>• Following a complete break >1cm → axons merely form a neuroma (a local swelling)<br></br>• Neuroma can cause severe pain<br></br>• However if a track is present → regeneration can occur for many centimetres (albeit slowly)
What glial cells in PNS promote axon regeneration?
Schwann cells
What glial cells remyelinate axons after peripheral nerve damage?
Schwann cells
What is Cajal’s Harsh Decree?
Axons cannot regenerate >1mm in CNS
What glial cells in CNS inhibit axon regeneration?
Oligodendrocytes<br></br>Astrocytes
What factors make adult CNS non-permissive for axon growth?
- ECM <b>lacks growth promoting molecules</b> (e.g. laminin)<br></br>2. <b>Oligodendrocytes</b> express <b>Nogo</b> (growth inhibitory)<br></br>3. <b>Astrocytes</b> produce <b>growth-inhibitory chondroitin sulphate proteoglycans (CSPGs)</b> + form <b>glial scar</b> that causes growing axons to stop
What is a scar in the CNS called?
Glial scar (caused by astrocytes)
What cells produce Nogo?
Oligodendrocytes
What are possible strategies for repair of CNS?
“1) Block Nogo<br></br>2) Peripheral nerve graft<br></br>3) Schwann cell graft<br></br>4) Neurotrophic factors<br></br>5) Blocking inhibitory proteoglycans<br></br>6) Neural grafting (foetal cells)<div><br></br></div><div><img></img></div>”
How does rehabilitation following nerve damage work?
Depends on promoting spouting of intact axons (plasticity)
Example of ischaemic nerve injury
Stroke<br></br>Mechanism of injury = mainly excitotoxic → ↑ intracellular Ca²⁺ which damages or kills neurons
Examples of neurodegenerative diseases
Parkinson’s, Alzheimer’s, MS
Where do stem cells exist in fetal brain?
Venticular and subventricular zone
Where do stem cells exist in adult brain?
1) Olfactory bulb<br></br>2) Dentate gyrus granule cells in the hippocampus
