NGD 1

Question 1

The majority of PD is idiopathic what does this mean and what are the thought causes?

Answer 1

Occurs sporadically, metals, recreational drugs such as (MPPP), toxins (pesticides).

Question 2

Familal PD

Answer 2

5-10%, autosomal recessive or dominant with a number of genes identified.

Question 3

What characterises PD?

Answer 3

Reduction in the Dopaminergic neurons within the SN.

Question 4

Compare what happens with the dopaminergic fibres in the substania nigra and the putamen?

Answer 4

50% of dopaminergic fibres in the putamen at diagnosis, continual loss over the next few years stabilsing 4 yrs post diagnosis and then stable decline. In the substania nigra you get 50-90% loss of tyrosine hydroxylase positive neurons at diagnosis and only marginal further loss.

Question 5

What are the putaminal/substantia nigra neurons stained with and why?

Answer 5

Tyrosine hydroxylase stained- which is invovled in the synthesis of dopamine.

Question 6

Name the vesicle transported and the dopamine transported?

Answer 6

VMAT, DAT.

Question 7

What are the pathways involved?

Answer 7

Mesolimbic Pathway
– Associated with pleasure, reward and goal directed behavior
• Mesocortical Pathway
– Associated with motivational and emotional responses
• Nigrostriatal Pathway
– Involved in coordinaton of movement (part of basal ganglia motor loop)
• Tuberoinfundibular Pathway
– Regulates secreton of prolactin by pituitary gland and involved in maternal behavio

Question 8

What affects the rate of production of dopamine

Answer 8

Rate of synthesis is regulated by:
–  Catecholamines as inhibitors of tyrosine
hydroxylase
–  Availability of Tetrahydrobiopterin
–  Presynaptic DA receptors
–  Activity in nigrostriatal pathway

Question 9

What is the function of dopamine.

Answer 9

• Controls voluntary movement (walk and reach out and grab something)
• Produces NT dopamine
• Dopamine regulates mood

Question 10

Where is the substantia nigra located?

Answer 10

Midbrain

Question 11

What does the SN project to and what are the 2 types?

Answer 11

Projects to striatum, forms part of the basal ganglia has pars compatica (large pigmented neurons with neruomelanin (oxidised polymer of dopamine)- main projetion to striatum, pars reticula (unpigmented)

Question 12

What is the BG?

Answer 12

Collection of nuclei (cluster of neurons in white matter of SC.

Question 13

Where are neurons lost in PD?

Answer 13

They are lost in the ventrolateral side of the nigrostriatal pathway projecting to the caudate and putamen

Question 14

Lewy bodies?

Answer 14

Appears in 5-20% of non symphomatic individuals aged 60 years and over- can occur in the absence of gliosis and neuronal loss thought to be preclinical

Question 15

Describe the role of alpha synuclein

Answer 15

inked to learning, development and synaptic plasticity associated with vesicles - possible regulator of vesicular transport and dopamine release