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Neuro > Biochemical Features of Neurons > Flashcards

Biochemical Features of Neurons Flashcards

1
Q

Do neurons require lots of energy to function?

A

Yes

75% of the energy from the brain is used by neurons

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2
Q

What factors are essential to prevent brain damage?

A

Oxygen/glucose supply

Mitochondria

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3
Q

Why are efficient transport mechanisms required for correct neuronal function?

A

The cell body can be over 1 metre away from the synapses

So efficient transport is required between compartments for correct neuronal function

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4
Q

Active synapses need (2 things):

A
  • mitochondria to be sent to them for energy

- report back to nucleus to synthesise new proteins/lipids for maintenance/growth of neurons

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5
Q

What percentage of all body energy does the brain consume?

A

20%

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6
Q

Which cells use up most of the energy in the brain?

A

Neurons - 75%

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7
Q

What is the main process by which neurons obtain ATP?

A

Oxidative phosphorylation

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8
Q

What is the main process by which astrocytes obtain ATP?

A

mainly glycolysis

can also give the end point of glycolysis straight to the neurones into the Krebs Cycle

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9
Q

Compare the number of ATP molecules made by oxidative phosphorylation to that made via glycolysis

A

2ATP vs 30-36 ATP

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10
Q

What structures produce ROS during ATP formation?

A

The ETC of mitochondria

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11
Q

What effect do ROS have on the mitochondria?

A

They damage mitochondria and other molecules

Lead the damaged mitochondria to be degraded by autophagy

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12
Q

After how long does lack of oxygen cause brain damage?

A

5 min

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13
Q

Describe the effect of NO on the ETC

A

Nitric Oxide (NO) inhibits the ETC reversibly by competing with O2

Or irreversibly through oxidation of complexes

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14
Q

What does NO make when it reacts with ROS?

A

Peroxynitrite

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15
Q

When is NO increased?

A

During neuroinflammation and stroke

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16
Q

Why do people with a stoke get worse 6 hours after the stroke?

A

Because of the high NO production

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17
Q

What is MPTP?

A

A heroin derivative toxin that inhibits complex I and induces Parkinsonian features in humans

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18
Q

In which diseases can ETC inhibition be found?

A

Parkinson’s, Alzheimer’s, Huntington’s

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19
Q

What aspect of neurons provides challenges compared to other cells, explain?

A

Their polarised nature

The cell body containing nucleus, ER can be over a meter away from the synapse

Functions in synapse very different to cell body

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20
Q

Compare the cell body to the synapse of the neurone

A

Cell body:
•Nucleus
•ER and protein synthesis
•Lysosomes for degradation of organelles and proteins, lipids

Synapse:
•Most mitochondria are in the synapse and have to move to centre to be degraded
•High mito ATP requirements
•Calcium spikes - vesicle release
•Exposure to growth/survival factors e.g. NGF (neurotrophins), BDNF for synaptic plasticity
•Plasticity of connections

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21
Q

What does anterograde axonal transport do?

A

Supplies newly synthesised proteins and organelles to maintain synaptic activity and growth cones to carry on growing

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22
Q

What does retrograde axonal transport do?

A

Removes old/damaged proteins and organelles from synapse for degradation; neurotrophic and injury-response signalling

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23
Q

What does fast axonal transport carry (in general)?

A

Membranous organelles and ribonucleoproteins

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24
Q

What are ribonucleoproteins?

A

Proteins carrying RNAs

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25
Q

Give examples of molecules carried by fast axonal transport

A
  • Mitochondria
  • Autophagosomes
  • Signalling endosomes
  • Lysosomes
  • Neurotrophic vesicles (e.g. BDNF)
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26
Q

Which direction does fast axonal transport go?

A

Both anterograde and retrograde

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27
Q

How fast is fast axonal transport?

A

1 – 3 micrometer/second

28
Q

What does new evidence suggest about the location of synthesis of some proteins in the neurons?

A

They are made in the axon/synapse

29
Q

What does slow axonal transport carry?

A

Cytosolic proteins and cytoskeleton

30
Q

Give examples of things carried by slow axonal transport

A

Subunits of neurofilaments

Microtubules

Actin

31
Q

Which direction dows slow axonal transport go in?

A

Anterograde only

32
Q

What is the speed of slow axonal transport?

A

0.2 – 2.5 mm/day

33
Q

List the components of axonal transport and what they are made of

A
  1. Cytoskeleton: microtubules
  2. Molecular motors: dynein and kinesin
  3. Cargo-specific proteins: e.g. miro for mitochondria
34
Q

What are microtubules?

A

Long scaffolds that extend from one end of neuron to the other

35
Q

What are microtubules composed of?

A

A and β-tubulin subunits polymerizing alternately to form protofilaments

36
Q

Describe the arrangement of a microtubule

A

13 protofilaments arranged in to helical cylinders

37
Q

Are microtubules polar - explain?

A

Yes

Negative end orientated towards cell body

Positive end extends down axons, dendrite

38
Q

Which end do microtubules grow towards?

A

The positive end

39
Q

Which kinds of transport are microtubules used for?

A

Both fast and slow

40
Q

Which molecular motors are responsible for anterograde movement?

A

Kinesin-family

41
Q

Which molecular motors are responsible for retrograde movement?

A

Dynein ( theres only one)

42
Q

Which molecular motors require ATP?

43
Q

Which end of the protofilament do kinesin-family motors go towards?

44
Q

Which end of the protofilament does dynein go towards?

45
Q

How many kinesins are expressed in the brain?

46
Q

Which type of molecular motors are simpler?

47
Q

What are molecular motors regulated by?

A

Kinases, phosphates and scaffolding proteins

48
Q

What are cargo-specific proteins?

A

They are proteins which bind to the end of the microtubules opposite to the molecular motor

Specific for certain structures

49
Q

What does miro bind to?

A

Mitochondria

50
Q

Why do mitochondria have to be transported to synapses?

A

Because growth cones and synapses have high energy demands

51
Q

In vivo what percent of mitochondria are mobile?

52
Q

Which directions do mitochondria move in?

A

Both directions

70% bias for anterograde

53
Q

What is mitochondrial movement dictated by?

A

Neuronal activity

54
Q

How exactly does high neuronal activity affect mitochondria?

A

High neuronal activity = high local calcium levels due to synaptic vesicle release

Mitochondria become immobilised in areas of high calcium

Mediated by miro which causes the mito to uncouple from the motor when there is high Ca

55
Q

What allows miro to affect mitochondrial transport?

A

Has two Ca++ binding domains that tell kinesin to stop

56
Q

What do NGF and BDNF stand for?

A

Nerve growth factor

Brain derived neurotrophic factor

57
Q

What is neuronal survival/synaptic maintenance mediated in part by ?

A

Neurotrophins: NGF, BDNF

58
Q

Which receptors do neurotrophins bind to?

A

p75 and Trk

59
Q

How do neurotrophins affect neurones?

A

Neurotrophins bind receptors on presynaptic membranes

Are transported back to the nucleus via signalling endosomes to affect transcription.

60
Q

What is autophagy?

A

An essential process for degrading aggregated/damaged proteins, lipids, and damaged organelles such as mitochondria.

61
Q

How does autophagy work?

A

Protein and organelles packed in to autophagosomes (double membrane) and taken back to soma where then can fuse with lysosomes for degradation

62
Q

What are hereditary spastic paraplegias?

A

Genetic mutations cause distal neuropathy of longest corticospinal tract neurons (spine to toe)

Get progressive weakness and spasticity

63
Q

What kinds of genes are mutated in hereditary spastic paraplegias ?

A

Those involved in axonal trafficking

64
Q

Which genes are affected in hereditary spastic paraplegias and what do they do ?

A

Spastin (SPG4) – involved in microtubule dynamics

KIF5a (SPG10) – Kinesin motor

KIF1A (SPG30) – kinesin motor

65
Q

Which diseases are problems with axonal transport implicated in?

A

Alzheimer’s

Parkinson’s

Huntington’s

Amyotrophic Lateral Sclerosis

Neuro (23 decks)

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