PD Animal Models

Question 1

What are the two main categories of animal models of PD?

Answer 1

Toxin based

Gene based

Question 2

Which toxin based models exist?

Answer 2

6-OHDA
Paraquat
Rotenone
MPTP

Question 3

Which gene based models exist?

Answer 3

Synuclein

Parkin

Question 4

What is 6-OHDA induced toxicity specific for?

Answer 4

DA neurons

Question 5

How does 6-OHDA attack DA neurons?

Answer 5

Accumulates in cytosol to generate ROS
AND
Inhibits complex I

Question 6

Describe 6-OHDA induced toxicity in the SNpc

Answer 6

Moderate but specific DA neuron depletion

Question 7

What are the pros oft he 6-OHDA model of PD?

Answer 7

Good at testing new drug

Question 8

What are the cons of 6-OHDA model?

Answer 8

May differ form humans

No Lewy body formation

Question 9

What is MPTP?

Answer 9

Neurotoxin

Question 10

How is the MPTP model of PD similar to human?

Answer 10

Preferential degeneration of putamen DA nerve
Cell loss in SNpc > VTA
DA neuromelanin cells are more susceptible to damage

Question 11

How is the MPTP model of PD different to humans?

Answer 11

Only damages DA

No lewy body formation

Question 12

What are MPTP models used for?

Answer 12

Novel drug treatment

Question 13

Outline MPTP metabolism

Answer 13

Crosses BBB
Converted to NPDP+ but MAO-B in non-DA cells
Then to MPP+
MPP+ released from glial cells to take up DA
But then also take up MPP+

Question 14

Why is it bad that cells take up MPP+?

Answer 14

Inhibits complex I to cause damage

Question 15

What is paraquat?

Answer 15

Herbicide

Question 16

Why is paraquat toxic if it doesn’t cross the BBB?

Answer 16

Forms superoxide radical to cause SNpc DA degeneration

Also a/w alpha-synuclein inclusions

Question 17

What are the pros of paraquat models of PD?

Answer 17

Useful to study alpha-synuclein role in PD

Question 18

What are the cons of paraquat models of PD?

Answer 18

Not known if it is selective for DA

Question 19

What is the difference between MPP+ and paraquat?

Answer 19

The second N-methyl-pyridinium group
MPP+ - phenyl group
Paraquat - paraquat group

Question 20

What is rotenone?

Answer 20

Widely used insecticide and fish poison

Question 21

What do rotenone treated rodents develop?

Answer 21

DA degeneration
Alpha-synuclein inclusions
Abnormal posture
Slowness of movement

Question 22

What are the pros of rotenone models?

Answer 22

Good for studying relationships between aggregate formation and cell death

Question 23

What are the cons of rotenone models?

Answer 23

Not selective to DA

Question 24

Describe the “quaking mouse mutant”

Answer 24

Spontaneous deletion of parkin
Leads to myelin deficiency and enhanced DA metabolism
Have tremor and behavioural defects

Question 25

Describe Parkin KO mice

Answer 25

Progressive motor anomlies
Sensorimotor integration
But increased DA release?

Question 26

What is 6-OHDA

Answer 26

Synthetic neurotoxic compound which selectively attacks DA neurons

Question 27

How does rotenone work?

Answer 27

Interferes with the electron transport chain via complex I inhibition

Question 28

Why does rotenone make a good model of PD?

Answer 28

Complex I is inhibited in PD b peroxynitrite

Question 29

How does paraquat work?

Answer 29

Accepts electrons and transfers them to molecular oxygen to create ROS