Neurotrophins

Question 1

trophic interactions

Answer 1

neuronal interactions lasting days/even a lifetime

Question 2

bueker 1948

Answer 2

trying to increase target tissue for innervation was injecting sarcoma tissue into chick embryos

Question 3

result of sarcoma 180

Answer 3

huge neuronal response only on side with tumour tissues
enlarged sympathetic chain and sensory ganglia
motor nerves unaffected

Question 4

What indicated vascular link?

Answer 4

same enlarged ganglia when add tumour to egg membrane

molecule/protein secreted

Question 5

Rita Levi-Montalcini

Answer 5

Nobel prize

discovery of NGF

Question 6

how to tell if active element was protein or nucleic acid

Answer 6

snake venom - phosphodiesterase break down nucleic acid

Question 7

mammalian equivalent of venom glands

Answer 7

salivary glands

Question 8

NGF

Answer 8

3 subunits

alpha, beta and gamma

Question 9

what subunit of NGF promotes outgrowth and survival?

Answer 9

beta

Question 10

what does b subunit of NGF affect?

Answer 10

sympathetic chain and subpopulation of sensory neurones

Question 11

2 reasons for neurons dying

Answer 11

normally in development and if no targets

Question 12

inject NGF into embryos - effect on neurons which would have died

Answer 12

rescues sympathetic and sensory neurons which would have died
NGF act as target-derived neurotrophic factor

Question 13

inject ab to NGF in embryo

Answer 13

total loss of sympathetic neurons

Question 14

NGF mRNA in target tissue

Answer 14

present in limited supply

direct relationship of NGF and sympathetic innervation

Question 15

NGF guidance role

Answer 15

sensory growth cones turn towards it in minutes

Question 16

inject NGF into brainstem of baby rat

Answer 16

sympathetic axons from ganglia grow back into spinal cord and up dorsal columns

Question 17

problem with NGF guidance role experiments

Answer 17

concentrations not physiological

Question 18

NGF - possible role, not guidance but?

Answer 18

NGF and receptors present only after axons enter target tissue
might keep neurones in

Question 19

3 chamber culture experiment

Answer 19

NGF in all 3 = grow
remove from b or c = end of axons whither
remove from cell body = axons and cell bodies okay

Question 20

findings from 3 chamber culture experiment

Answer 20

terminal endings maintained locally and peripheral neurites support cell body
retrograde transport of NGF

Question 21

2 classes of NGF receptors

Answer 21

trkA = high affinity 
trkB = low affinity

Question 22

trkA critical for?

Answer 22

survival and outgrowth promotion

Question 23

trka receptor

Answer 23

dimerises - binds and activates 2 tyrosine kinase molecules in cytoplasm and autophosphorylate

Question 24

does NGF enter nucleus?

Answer 24

no
1. anti NGF into cell body - no affect on activity
2. NGF into cell body - not active
retogradely transported - may activate secondary messenger

Question 25

basal forebrain nuclei project where?

Answer 25

cortex and hippocampus

Question 26

what do basal forebrain regions contain?

Answer 26

mRNA for NGF

Question 27

what do basal forebrain neurons express?

Answer 27

trkA

Question 28

NGF - alzheimers

Answer 28

loss of cholinergic forebrain neurons and NGF infusion can improve learning and memory - save cholinergic neurons from cell death

Question 29

when was 2nd neurotrophin found? what was it?

Answer 29

1982, BDNF

Question 30

% homology BDNF and NGF

Answer 30

50

Question 31

BDNF

Answer 31

supoprts survival and promotes outgrowth of some sensory neurones and motor neurones

Question 32

other neurotrophins with separate neuronal specificites

Answer 32

NT3, NT4/5

Question 33

BDNF receptor

Answer 33

low affinity NGF receptor - p75

Question 34

high affinity receptor for other neurotrophins

Answer 34

bdnf and nt4/5 = trkb | bt3 = trkc

Question 35

where is trkA mRNA localised to?

Answer 35

selected PNS/CNS sites - restricted activities for NGF

Question 36

trkB and trkC distribution

Answer 36

them and their ligands wider distribution - wider influence than NGF

Question 37

truncated trkb and c

Answer 37

no cytoplasmic signalling domain | widespread in CNS and also in astrocytes

Question 38

functions of truncated trkb and c

Answer 38

high local concetration of growth factor by sequestering on cell surface may internalise and degrade

Question 39

NGF and trkA KO

Answer 39

dramatic loss of DRG neurones a birth | almost no sympathetic neurons

Question 40

NGF and trkA KO - sensory neurones lost?

Answer 40

small peptidergic - pain/thermal perception

Question 41

nociceptors and NGF

Answer 41

rely on NGF for survival

Question 42

mice overexpressing NGF and pain

Answer 42

hyperalgesic

Question 43

trkB-/-

Answer 43

do not feed and die

Question 44

BDNF -/-

Answer 44

behavioural phenotype | head bobbing/spinning - lost 90% vestibular axons - all require BDNF

Question 45

motor neurones BDNF and trk4/5

Answer 45

trkB-/- = significant loss BDNF -/- = no motor neurone loss Nt4/5 more important

Question 46

what neurones are nt3 dependent?

Answer 46

1a afferents from muscle spindle

Question 47

nt3 or trkc KO

Answer 47

abnormal posture/movements | similar to pseudoathetosis - large fibre neuropathy

Question 48

nt3 - muscle spindle

Answer 48

development fails as induced by 1a sensory nerves | no golgi tendon organs as 1b missing too

Question 49

``` Fill in the gaps:- sympathetic neurones depends on pain/temp sensory neurones vestibular sensory neurones proprioceptive sensory neurones ```

Answer 49

NGF NGF BDNF NT3

Question 50

Problem with use for clinical therapies?

Answer 50

BBB

Question 51

CTNF

Answer 51

ciliary neurotrophic factor