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Developmental Neuroscience > Neurotrophins > Flashcards

Neurotrophins Flashcards

1
Q

trophic interactions

A

neuronal interactions lasting days/even a lifetime

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2
Q

bueker 1948

A

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

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3
Q

result of sarcoma 180

A

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

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4
Q

What indicated vascular link?

A

same enlarged ganglia when add tumour to egg membrane

molecule/protein secreted

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5
Q

Rita Levi-Montalcini

A

Nobel prize

discovery of NGF

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6
Q

how to tell if active element was protein or nucleic acid

A

snake venom - phosphodiesterase break down nucleic acid

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7
Q

mammalian equivalent of venom glands

A

salivary glands

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8
Q

NGF

A

3 subunits

alpha, beta and gamma

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9
Q

what subunit of NGF promotes outgrowth and survival?

A

beta

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10
Q

what does b subunit of NGF affect?

A

sympathetic chain and subpopulation of sensory neurones

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11
Q

2 reasons for neurons dying

A

normally in development and if no targets

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12
Q

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

A

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

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13
Q

inject ab to NGF in embryo

A

total loss of sympathetic neurons

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14
Q

NGF mRNA in target tissue

A

present in limited supply

direct relationship of NGF and sympathetic innervation

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15
Q

NGF guidance role

A

sensory growth cones turn towards it in minutes

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16
Q

inject NGF into brainstem of baby rat

A

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

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17
Q

problem with NGF guidance role experiments

A

concentrations not physiological

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18
Q

NGF - possible role, not guidance but?

A

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

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19
Q

3 chamber culture experiment

A

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

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20
Q

findings from 3 chamber culture experiment

A

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

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21
Q

2 classes of NGF receptors

A 
trkA = high affinity 
trkB = low affinity
22
Q

trkA critical for?

A

survival and outgrowth promotion

23
Q

trka receptor

A

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

24
Q

does NGF enter nucleus?

A

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

25
Q

basal forebrain nuclei project where?

A

cortex and hippocampus

26
Q

what do basal forebrain regions contain?

A

mRNA for NGF

27
Q

what do basal forebrain neurons express?

A

trkA

28
Q

NGF - alzheimers

A

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

29
Q

when was 2nd neurotrophin found? what was it?

A

1982, BDNF

30
Q

% homology BDNF and NGF

A

50

31
Q

BDNF

A

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

32
Q

other neurotrophins with separate neuronal specificites

A

NT3, NT4/5

33
Q

BDNF receptor

A

low affinity NGF receptor - p75

34
Q

high affinity receptor for other neurotrophins

A

bdnf and nt4/5 = trkb

bt3 = trkc

35
Q

where is trkA mRNA localised to?

A

selected PNS/CNS sites - restricted activities for NGF

36
Q

trkB and trkC distribution

A

them and their ligands wider distribution - wider influence than NGF

37
Q

truncated trkb and c

A

no cytoplasmic signalling domain

widespread in CNS and also in astrocytes

38
Q

functions of truncated trkb and c

A

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

39
Q

NGF and trkA KO

A

dramatic loss of DRG neurones a birth

almost no sympathetic neurons

40
Q

NGF and trkA KO - sensory neurones lost?

A

small peptidergic - pain/thermal perception

41
Q

nociceptors and NGF

A

rely on NGF for survival

42
Q

mice overexpressing NGF and pain

A

hyperalgesic

43
Q

trkB-/-

A

do not feed and die

44
Q

BDNF -/-

A

behavioural phenotype

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

45
Q

motor neurones BDNF and trk4/5

A

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

46
Q

what neurones are nt3 dependent?

A

1a afferents from muscle spindle

47
Q

nt3 or trkc KO

A

abnormal posture/movements

similar to pseudoathetosis - large fibre neuropathy

48
Q

nt3 - muscle spindle

A

development fails as induced by 1a sensory nerves

no golgi tendon organs as 1b missing too

49
Q 
Fill in the gaps:-
sympathetic neurones depends on 
pain/temp sensory neurones
vestibular sensory neurones
proprioceptive sensory neurones
A

NGF
NGF
BDNF
NT3

50
Q

Problem with use for clinical therapies?

A

BBB

51
Q

CTNF

A

ciliary neurotrophic factor

Developmental Neuroscience (10 decks)

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