Neuronal Cell survival morphogenesis

Question 1

What is the thumb rule that serves at estimating the number of neurons that will undergo programmed cell death?

Answer 1

In the nervous system, cell death matches the number of neurons with the size of the target innervated.

Question 2

What are the 4 classic morphological features of apoptosis?

Answer 2

1. Cell and nuclear shrinkage;
2. Condensation of chromatin + DNA fragmentation;
3. Cell is ripped appart in packages (apoptotic bodies);
4. Phagocytosis of apoptotic bodies.

Question 3

How are apoptosis and necrosis inductions differentiating?

Answer 3

Apoptosis is caused by the activation of an active biochemical program that requires mRNA and protein synthesis.

Necrosis is independent of cell activity and is most likely caused by traumatic cellular damage and lysis.

Question 4

What secondary biological response is unique to necrosis?

Answer 4

Inflammation.

Question 5

What is the advantage for cells undergoing apoptosis to splinter in apoptotic bodies?

Answer 5

Minimize contamination of neighbouring cells and easy to disintegrate for macrophages.

Question 6

Why is it essential that neurons undergo apoptosis?

Answer 6

Neurons are generally overproduced. For cost-efficient innervations of their respective targets, neurons must be pruned.

Question 7

What experiment using the chick embryo could hint at a correlation between target size/activity and neuronal survival?

Answer 7

Removal of a limb bud decreases the survival rate of its respective innervating motor neuron population. Transplantation of an extra limb bud increases the survival rate of its respective innervating motor neuron population.

Question 8

If paralyzing a chick embryo limb bud by blocking its muscle activity with curarae, what do you predict for the survival rate of its innervating motor neuron population. What does that suggest?

Answer 8

Survival rate is increased compared to control (75% instead of 50% survive). This suggests that muscle activity turns down the expression of a trophic factor by the muscle, which makes the competition for trophic support more intense, thereby fine tuning the innervation.

Question 9

What is the ultimate objective of a neurotrophic system?

Answer 9

Matching the number of neurons to the size/activity of the target tissue.

Question 10

What is the difference between a tropic and a trophic factor?

Answer 10

Tropic factors are involved in axon guidance, while trophic factors are involved in cell survival.

Question 11

What happens to neurons not provided enough neurotrophic factors?

Answer 11

Undergo apoptosis.

Question 12

True or false: NGF is necessary but not sufficient to promote survival of DRG sensory neurons and their outgrowth.

Answer 12

False: it is sufficient.

Question 13

What happens if a NGF antiserum is injected in vivo?

Answer 13

The region targeted by the antiserum loses its NGF trophic support and a large portion of its neuronal populations undergoes apoptosis.

Question 14

True or false: NGF is a dimer complex.

Answer 14

True.

Question 15

What subunit of NGF complex is responsible for the trophic support?

Answer 15

Beta.

Question 16

Name a member of the neurotrophin family that is found in the brain.

Answer 16

BDNF.

Question 17

What does account for extensive number of functions that can accomplish neurotrophins?

Answer 17

The diversity of receptors to which they bind.

Question 18

When knowing about the mechanism of activation of Trk receptors, why does it make sense that NGF is a dimer?

Answer 18

Trk receptors activate upon dimerization. Trk receptors dimerize because their ligands (NGF, e.g.) are dimers themselves, allowing two Trk receptors to crosslink and phosphorylate each other.

Question 19

How would the activity of Trk receptors be modulated by the binding of a monomeric neurotrophin?

Answer 19

The receptors would be silenced because they could not dimerize and activate.

Question 20

To which neurotrophins does receptor p75 bind? Why is it said that receptor p75 balances the activity of Trk receptors?

Answer 20

Receptor p75 binds to every neurotrophin. Its activity is considered antagonistic to Trk’s because p75 contains a death domain intracellularly, which promotes cell death upon ligand binding. Trk and p75 receptors therefore balance out each other.

Question 21

In order of transduction, list the players involved in the intracellular cascade provoked by Trk activation.

Answer 21

Tyrosine kinases on the intracellular domains of Trk receptor -> Shc -> Grb2 -> Sos -> Ras -> Raf -> MEK -> ERK -> nucleus or phosphorylation of cytoplasmic proteins

Question 22

Neurotrophins recruit which intracellular pathways to promote cell survival?

Answer 22

Activation of PLCgamma + PI3 kinase ->Akt (PKB) ->Bcl2 ->inhibition of apoptosis state.

Question 23

In the apoptotic signal transduction, how are the Bcl-2, Ced-4 and Caspase families relating?

Answer 23

Bcl-2 inhibits Ced-4, and Ced-4 activates Ced-3 (-> apoptosis). Therefore, relieving the inhibition of Bcl-2 (by inhibiting it) triggers apoptosis.

Question 24

In the apoptotic signal transduction, activation of which step is considered the point of no return in terms of cell survival?

Answer 24

Activation of caspases.

Question 25

True or false: NGF causes the intracellular inhibition of Bcl-2, preventing apoptosis induction.

Answer 25

False: NGF causes the intracellular activation of Bcl-2, strengthening Ced-4 inhibition.

Question 26

Why is the Campenot Chamber a useful tool for studying neurotrophic activity? What was demonstrated with it?

Answer 26

The Campenot Chamber allows to have cells bodies and their axons in different chambers (different solutions). It was used to demonstrate that neurite growth can be locally (axons) controlled by neurotrophins.

Question 27

How can neurotrophins bound on Trk receptors of axons regulate cell survival if this pathway requires the cell body (DNA), which can be very distant from the local action of neurotrophin signaling?

Answer 27

Neurotrophin-bound Trk receptors can be retrogradely transported to the nucleus via vesicle carriage.

Question 28

True or false: trophic factors can also be autocrine.

Answer 28

True.

Question 29

What considerable advantage do steroid hormones regulating neuronal growth have over other neurotrophins?

Answer 29

Due to their lipid composition, steroid hormones can readily pass through the plasma membrane and directly bind to receptors in the cytoplasm.

Question 30

What could account for sexually dimorphic differences in certain neuronal circuits?

Answer 30

Hormone steroids like estrogen and testosterone.