2 - Neurodegeneration in the Basal Ganglia

Question 1

Pathology of Parkinsons

Answer 1

Loss of dopaminergic cells (black) in substantia nigra pars compacta
Presence in neurons of Lewy bodies

Question 2

Lewy bodies

Answer 2

Intracellular formations enriched in the protein α-synuclein

Also found in dementia

Question 3

Striatum

Answer 3

Caudate and Putamen

Inhibitory to thalamus

Question 4

Direct Pathway

Answer 4

Gpi –> Thalamus –> Cortex

Question 5

Indirect Pathway

Answer 5

Gpe –> STN –> Gpi

Question 6

What happens in the pathways in parkinsons

Answer 6

Indirect pathway much more active and direct pathway less active
Thalamus inhibited so Less excitatory drive to the motor cortex

Question 7

Imaging

Answer 7

Dopaminergic cell loss via Dopamine transporter imaging (DaT0

Question 8

What can you use to label the projections of DaT scan

Answer 8

SPECT ligands

Question 9

Motor features of parkinsons

Answer 9

o Resting tremor, bradykinesia (akinesia), rigidity
o Frozen facial expression
o Flexed posture
o Altered gait and postural changes
o Difficulty in initiating and stopping movement

Question 10

Non-motor features

Answer 10

	olfactory dysfunction
	depression
	psychotic symptoms
	cognitive dysfunction
	dementia (late phase)

Question 11

How many years do non motor symptoms precede parkinsonian motor symptoms

Answer 11

12-15 years

Question 12

How do you score parkinsosn

Answer 12

Schwab and England Activities of Daily living

Question 13

Most common genes associated with parkinsosn

Answer 13

LRRK2

Question 14

Which gene codes for protein alpha-synuclein

Answer 14

SNCA

Question 15

MPTP

Answer 15

A drug which is metabolised into MPP+ which is neurotoxic to do dopaminergic neurons

Question 16

What no. complex of the mitochondrial respiratory chain when dysfunctioned can lead to oxidative stress

Answer 16

Complex I

Question 17

What are the precursors of dopamine

Answer 17

Ltyrosine -> L-Dopa -> dopamine

Question 18

What is dopamine oxidised to

Answer 18

Dopamine -> DOPAC -> Homovannilic acid

Question 19

What are the 3 dopaminergic pathways in the CNS

Answer 19

 Mesocortical
 Mesolimbic
 Nigrostriatal

Question 20

Dopamine receptors

Answer 20

GPCR

Question 21

D1 receptor subtypes

Answer 21

D1

D5

Question 22

D2 receptor subtypes

Answer 22

D2
D3
D4

Question 23

L-DOPA

Answer 23

Levodopa

Question 24

What is LDOPA combined with

Answer 24

DOPA decarboxylase inhibitor

Question 25

DOPA decarboxylase inhibitor

Answer 25

Carbidopa | Benserazide

Question 26

Adverse effects of L-DOPA

Answer 26

Nausea, impulse control disorders, postural HT On off effect, wearing off dyskinesia, dystonia

Question 27

Dopaminergic Agonists

Answer 27

ropinirole, pramipexole, rotigotine, pergolide, bromocriptine, cabergoline

Question 28

Rotigotine

Answer 28

Transdermal Patch

Question 29

Apomorphine

Answer 29

Infusions

Question 30

MAOB inhibitors

Answer 30

• Rasagiline, selegiline

Question 31

Anticholinergic (antimuscarinic) compounds

Answer 31

Orphenadrine, procyclidine, trihexyphenidyl

Question 32

COMT inhibitors

Answer 32

• entacapone, tolcapon

Question 33

Which drugs can induce cardiac fibrosis

Answer 33

pergolide, cabergoline, bromocriptine

Question 34

Which chromosome is protein huntingin on

Answer 34

4

Question 35

What codon are the abnormal repeats (in huntingtons)

Answer 35

CAG | Glutamine

Question 36

What is the pathology of huntingtons

Answer 36

degeneration of striatal neurons cortical atrophy Loss of medium size spiny neurons (striato-pallidal and striato-nigral pathways) Intranuclear inclusions of huntingtin

Question 37

Cause of neurodegeneration in huntingtons

Answer 37

Excitotoxicity Aggregates of huntingtin Increased oxidative stress

Question 38

Why is there increased drive to the motor cortex in huntingtons

Answer 38

Destruction of striatum so both direct and indirect pathways are lost Increased thalamic drive so Increased drive to motor cortex

Question 39

Symptoms of huntingotns

Answer 39

Choreic movements gait abnormalities lack of coordination cognitive impairment

Question 40

Vesicular amine transporter inhibitor | HUNTINGTONS

Answer 40

tetrabenazine

Question 41

haloperidol, olanzapine

Answer 41

Anti-dopaminergic drugs to treat huntingotns

Question 42

Antidepressants for huntingtons

Answer 42

imipramine, amitriptyline