Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neurobiology of Disease > Exam 1: Parkinson's > Flashcards

Exam 1: Parkinson's Flashcards

1
Q

Lateral corticospinal tract

A

3/4 axons
cross MEDULLA
originate in cortex for LIMBS

terminate Lateral alpha-MN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Ventral Corticospinal tract

A

1/4 axons
axons don’t cross
originate cortex represents neck shoulder trunk
terminate MEDIAL alpha-MN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Transected pyramid tract

A

can stand walk run but can’t use hands/pick up objects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Motor cortex

A

collateral sent to

1) vestibular nuclei
2) superior colliculus
3) Reticular formation
4) Red nuceus
5) Cranial motor nuclei

to alpha MN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Local circuit neurons

A

reflex coordination
local grey matter spine circuit

to lower motor neuron pools to skeletal muscle

where sensory input comes in

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

upper motor neurons

A

essential for voluntary movement

integration of sensory and adjust reflex activity of spinal cord

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

basal ganglia

A

getting initiation of movement

no direct to local circuit and LMN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Cerebellum

A

sensory motor coordination

detects differences between actual and intentional movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does the globus pallidus and SN par reticulta inhibit? What is it in feedback loop with?

A

Superior colliculus and thalamus

Subthalamic nuc (feedback)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Basal ganglia structures: INPUT

A

1) Frontal cortex - primary and secondary motor association areas
2) Parietal cortex - secondary visual and somatic sensory
3) Temporal Cortex - visual auditory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Basal Ganglia: incoming axons

A

cortical glutaminergic

synapse on medium spiny neurons in striatum

Also receive DA input from SN pars compacta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Basal ganglia: medium spiny neuron projections

A

GABA projections

to GP and SN pars reticula

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Basal ganglia: GP and SNpr projections

A

inhibitory

through thalamic relay, directly to collicular N.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the pathway:

Striatum
GP
Thalamus
Cortex

A

Striatum: INhibits GP: Inhibits: Thalamus: Activates: crotex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

BG: direct pathway

A

D1 receptors from SN pars compacta

Caudate/putamen: inhibits INTERNAL GP

disinhibiting thalamus = INCREASED motor output

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

BG: indirect pathway

A

D2 receptors in SN pars compacta

EXTERNAL SEGMENT

GP inhibit Subthalamic nuc which activates internal segment (plot twist)

Now internal GP can inhibit Thalamus!
Decreased motor output

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Parkinson’s cause and demographics

A

2nd leading neurodegenerative disorder 1,000,000 in US, 5,000,000 worldwide

age is the greatest risk factor, typically 5th-7th decade

99% idiopathic (no known cause) some rare family forms

More common in Caucasian males

higher rise in rural areas (environment)
nicotine and caffeine protective.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Parkinson’s symptoms

A

tremor (resting)
rigidity: hands/feet
bradykinesia- slow movement, can’t start/stop movement
postural instability- balance/coordination

micrographia, sleep issue, dementia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Parkinson’s disease: premotor stage

A 
constipation
loss of smell
bad sleep 
acting out dreams
anxiety
executive function and attention issues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Parkinson’s: early stage

A

resting tremor, postural instability, bradykinesic, rigidity, levodopa typically effective at this point.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Parkinson’s: moderate

A

on/off periods, constipation, and depression common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Parkinson’s: advanced

A

gait worse, instability, falling issues, dementia and behavioral issues.

Residential nursing required. Life expectancy is near normal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Incidence/prevalence parkinson’s

A

inconsistent prevalence (environment factors)

age major risk factor, rare before 50

males more

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Brain of Parkinson’s: normal, but wait!

A

loss of pigmented dopaminergic in SN pars compacta, replaced by phagocytic cells, gliosis and astrocytes

Lewy bodies= aggregates of tau protein, alpha-synuclein, ubiquitin, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

alpha-syn

A

charperoning vesicles

if it can’t protein accumulation. SNCA involved too.

26
Q

what controls accumulation of protein?

A

ubiquitin and proteasome system and LAS system

27
Q

Parkinson’s is overactivation of the

A

INDIRECT pathway. thalamus inhibited. little motor output.

28
Q

Pathogenesis: neuromelanin

A

interactions between melanin and metals may produce free radical formation, resulting in mitochondrial function

Autoxidation, polymer pigment

29
Q

Pathogenesis: alpha-synuclein

A

mutations in presynaptic protein associated with microtubule dysfunction and amyloid fibril formation through interaction with tau

A3OP gene, 5% family

30
Q

Pathogenesis: Neurofilament

A

mutations in neurofilament proteins other than tau have been found in PD patients

31
Q

Pathogenesis: ubiquitin/proteasome pathway

A

ubiquitin tags misfolded or nonfunctioning proteins for degradation by proteasomes. Disruption of this pathway may result in intracellular protein accumulation.

Heat shock proteins

32
Q

D1

A

direct, increase cAMP

33
Q

D2

A

indirect decrease cAMP

34
Q

DA neurons have intrinsic rhythm which needs frequent depolarization. High energy consumption, active mitochondria. So what?

A

Lots of ROS, damages mitochondria membranes and DA

35
Q

Parkinson’s pathogenesis (stages)

A

Stage 1-2 Lewy bodies medulla and pons

Stage 3 aggregated alpha-syn in SN

Stages 4-6 supratentorial compartment in graded fashion

Substantial neocrotical pathology in stage 6 (cortex)

Pathology caudal –> Rostral

loss of 80%+ DA neurons in SN before symptoms

36
Q

What is main point of Parkinson genetics?

A

gradient of genes and environmental factors

LRRK2 (leucine)
alpha-synuclein SNCA 4q21
GBA: lysosomal enzyme
Microtubule-associated protein tau (MAPT)

37
Q

alpha-synuclein genetics

A

early on set.
dominant inheritance
SNARE complex issues- can’t assembly SNARE

38
Q

LRRK2 gene

A

arabs/Ashkenazi

autosomal dominant

late onset
protein-protein interaction

39
Q

Parkin gene

A

autosomal RECESSIVE PD.
encodes for ubiquitin ligase in protein degradation and recycling along ubiquitin-proteasome pathway

reduced protein degradation

40
Q

PINK1

A

abundant protein kinases

degrades failing mitochondria

recruits parkin to label for autophagic clearance by lysosomes. Recessive.

41
Q

Parkinson treatment list (4 different ones)

A

1) Thalamic DBS
2) Dopamine replacements anticholinergics, trophic factors cell transplants
3) Subthalmonotomy STN DBS (Gene therapy (GAD))
4) Gpi DBS pallidotomy

42
Q

Deep brain stimulation

A

in GP or Thalamus

Complication: executive function issues.

relieve tremor/dyskinesia

no effect on rigidity and bradykinesia

43
Q

Paper: Bilateral Deep Brain stimulation vs. Best medical therapy for patients with advance Parkinson disease

A

results: again 4.6 hours a day without dyskinesasia

motor function improvements
great ! of L-scale improvements

did have adverse effects and risk

Conclusion: good, but risk

Better motor control (handwriting)

44
Q

Levodopa

A

front line drug for parkinsons’

Combined with carbidopa, which reduces side effects, stops levodopa from getting in blood stream

45
Q

Dopamine agonists

A

supplement levodopa

may interact with other drugs

46
Q

anticholinergics

A

secondary meds (benzotropine mesylate)

47
Q

MAO =-B inhibitor and COMT

A

so DA not degraded
supplementary med

MAO: selegiline
COMT: entacapone

48
Q

problems with DA agonists?

A

unintended movement

hallucinations

49
Q

Physical therapy

A

exercise
stretching and strengthening
patterned movements (high stepping)

50
Q

Occupational Therapy

A

orthotic and adaptive equipment
home and workplace modification
speech therapy

51
Q

Neural grafting: rat paper in neostraitum

A

animal unilateral lesions, spin when given amphetamine, but grafts stop it

lesioned in niagral-striatal DA pathway with 6-OHDA

treated symptomatically, not curable

52
Q

Neural grafting: TH staining in striatum shows what?

Problem with placing grafts?

A

TH-immunoreactive cell-bodies in striatum

G1,3,4 cell bodies show TH-immune fiber network

SN graft fail to send axons to striatum

53
Q

MPPP vs. MPTP what is going on?

A

MPTP is impure, makes MPP+, DA neurotoxin.

Animal model

54
Q

Neural grafting: monkey

A

MPTP lesion in SN
Fetal monkey tissue

TH+ cells found after VM tissue engraphed

55
Q

Neural grafting: clinical trials

A

decreased rigidity, but mixed results

better in younger patients
trends, but no significant effect

some developed dyskinesia

56
Q

Gene therapy for Parkinson’s

A

adenvirus-free recombinant adeno-associated virus. Tranfected using 3 plasmids

1) plasmid with transgene
2) replication and capside genes
3) plasmid with adenovirus helper genes

generating Ad-free rAAV

57
Q

What is most common viral vector in parkinson’s

A

rAAV

58
Q

Types of gene therapy trials in progress for parkinsons’

A

1) enzyme replacement
2) BG circuit modification
3) Protection form disease with trophic factors

59
Q

Experiment: Primate Parkinson’s AAVV with dopamine synthesizing enzyme

A

genes for TH, AADC, GTP-cyclo in 3 different rAAV to MPTP

Result? Improvement

60
Q

Clinical Trials: Dopamine replacement

A

levtiviral prep (HIV): packaging ability

tropism= cells a virus can attach to and infect
pseudotyping- envelope characteristics

Some improvement

61
Q

Clinical trials: AAV to deliver AADC

A

inject to striatum

moderate improvement

Neurobiology of Disease (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions