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Neuro Quiz 6 > Pathophysiology of Parkinson's Disease > Flashcards

Pathophysiology of Parkinson's Disease Flashcards

1
Q

Parkinson’s disease is a

A

PROGRESSIVE and NEURODEGENERATIVE disorder with INSIDIOUS onset

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2
Q

Four Cardinal Signs of PD are:

A

Resting Tremor
Muscular rigidity
Bradykinesia
Postural impairment

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3
Q

As the disease progress, you could see

A

Issues arise with swallowing and speech

Insomnia and incontience

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4
Q

Declining NE levels can lead to

A

visual and heart disturbances + orthostatic hypotension

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5
Q

Mean age of onset

A

~60 years

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6
Q

The brain of a Parkinson’s patient shows

A

Dramatic loss of dopamine-containing neurons in the substantia nigra pars compacta

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7
Q

The SNpc sends axons to the

A

caudate adn putamen/striatum which is a part of the basal ganglia and involve din control of movement

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8
Q

The degree of functional impairment is correlated with

A

the loss of nigral neurons

Symptoms aren’t seen until 80% neuronal loss is approached

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9
Q

Basal ganglia regulates

A

size and volume of movement that occurs through the primary motor neurons

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10
Q

Define Lewy Bodies

A

Abnormal filamentous aggregates of the protein alpha-synuclein
Not specific for AD

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11
Q

Lewy bodies can be seen through

A

silver stain or eosin and are located in the presynaptic bouton where it regulates the function of synaptic vesicles

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12
Q

Lew bodies in PD

A

They precipitate into filaments and accumulate in the brain

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13
Q

Common theme of neurdegenerative disorders?

A

Selective neuronal vulnerability - something about the disease affects one type of neuron more than others

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14
Q

Substantia nigra has

A

Neuromelanin which is made from oxidized dopamine
High levels of FE which may enhance the oxidation of DA
Migroglial cells which produce ROS

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15
Q

Heritability for PD

A

0.17

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16
Q

Gene mutation in PD are

A

Mendelian and polygenic risk factors

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17
Q

Two Risk Factor Genes

A

GBA-acid beta-glucosidase

UbiquitinC-terminal esterase L1 (UCHL1

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18
Q

Other genetics in PD

A 
SNCA
PARK2
PARK7
PINK1
LRRK2
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19
Q

SNCA

A

Mutation in the gene encoding alpha-synuclein which is a major protein in lewy bodies

20
Q

PARK2

A

Encodes Parking an E3 ubiquitin ligase that recognizes damage and defective proteins and tags them for distruction
Also involved in mitophagy or removal of damaged mitochondria

21
Q

PARK 7

A

Encodes DJ1, a chaperone protein that protects damage proteins from misfolding
Function as a regulator of oxidant defenses

22
Q

PINK1

A

Recruits Parkin to damaged mitochondria to do its job

23
Q

LRRK2

A

Known to associate with Parkinson’s but unknown how

Leucine Rick Repeat Kinase-2 (dardarin)

24
Q

Environmental Toxins associated with PD

A

6- hydroxydopamine

MPTP

25
Q

6-hydroxydopamine

A

Produces ROS and is taken up by DA transporters into the neurons and wreck havoc

26
Q

MPTP

A

Once ingested, MAOB converts MPTP to MPP which does not cross the BBB but MPTP. It uses DA transpoter to get inside the cell and inhibits Mitochondrial Complex 1
No ATP then no cell

27
Q

Drug Induced PD

A

Antipsychotics (haldol)
Reserpine
Metoclopramide
Tetrabenzine

28
Q

Other disease that induced PD

A 
Progressive supranuclear palsy
Corticobasal degeneration
Shy-Drager syndrome
Alzheimer's
Wilson's disease
Creutzfeldt-Jakob
Striatonigral degeneration
Encephalitis (WW1)
29
Q

Toxin Induced PD

A

Flour made from cycad seed has beta-methylaminoalanie

Manganese, carbon disulfide, CO

30
Q

Trauma Induced PD

A

Dementia pugilistica (punch drunk)

31
Q

Tyrosine hydroxylase dose what

A

Tyrosine to DOPA with oxygen

32
Q

High levels of Fe(III) in SN neurons leads to

A

Reaction with neuromelanin to form Fe(II) which reacts spontaneously with H2O2 to from OH- (destorys SNA and crosslinking lipids)

33
Q

3-nitrotyrosine is seen when

A

NO reacts with OH- producing ONOO- which reacts with tyrosine in proteins = oxidative stress

34
Q

BG receives input from where and does what with it

A

Cerebral cortex, processes it and sends it back to premotor and motor cortex to modulate activity of cortical neurons which send signals to motor neurons in the ventral horn of the spinal cord

35
Q

Net effect of basal ganglia output neurons in the internal globus pallidus (IGP) is

A

INHIBITION of motor activty

36
Q

Direct Pathway

A

Acts on the output neurons of the IGP to reduce inhibition of the motor pathway

37
Q

Indirect Pathway

A

Sends axons from the stiatum to the EGP which is in the subthalamic nucleus which then sends axons to the output neurons in the IGP/SNR to reinforces inhibition of motor activity

38
Q

Direct pathway is characterized by

A

D1, substance P and dynorphin

39
Q

Indirect pathway is characterized by

A

D2 and enkephalin

40
Q

Basal ganglia sends innervation where else?

A

Frontal and limbic cortex for a role in cognitive and emotional behavior

41
Q

DA in the circult

A

DA neurons are pacemaker neurons that require lots of ATP

They cause a rise in Ca which further increases the ATP need so you need good mitochondria

42
Q

DA + Direct

A

Facilitates direct so increases motor activity

Through D1

43
Q

DA + Indirect

A

Inhibits indirect so increases motor activity through inhibition of indirect
Through D2

44
Q

Loss of DA in PD leads to

A

no thalamic activation of motor coretex

45
Q

ACh in the circut

A

Dopamine prevents the overactivation of cholinergic inhibitory neurons
With the loss of DA, these inhibitory neurons are hyperactive leading to overactivity of the indirect pathway = bradykinesia and muscle rigidity

46
Q

Nucleus Accumbus Function

A

Reward and Reinforcement and motivation

47
Q

Too much DA =

A

Psychosis – so correct DA deficiency in PD can lead to psychosis

Neuro Quiz 6 (2 decks)

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