Neuropathophysiology - Parkinson's Disease Flashcards
Disease of _______
lack of ______ in ______ area of brain
basal nuclei
dopamine
substantia nigra
2 things that characterize PD?
dopaminergic neuron loss
DA depletion
functions of basal nuclei? 3 main
inhibit unwanted movement
selecting purposeful movements
postural support
basal nuclei pathway:
- Direct pathway _____ thalamus (dMSN)
- Indirect pathway _____ thalamus (iMSN)
- SNc NT is _____, and SNc ______ the direct pathway while ____ the indirect pathway.
-excites
-inhibits
(normally these balance and work together)
-dopamine, excites direct, inhibits indirect
Be able to draw out circuit mechanism of PD for exam.
In PD model:
-dopaminergic neurons in _____ are lost
-leading to an imbalance between ____ and ____
-____ becomes more active
-_____ becomes less active
-leading to loss of _____ and occurrence of _______
-SNc
-dMSN and iMSN
-iMSN
-dMSN (less active_
-selective purposeful movement reinforcement;
unnecessary/unwanted movements
Molecular events underlying PD: Primary reasons of SNpc neuronal loss: -\_\_\_\_\_\_\_ -\_\_\_\_\_\_\_-impaired bio-energetics, oxidative stress Others: -\_\_\_\_\_\_ -\_\_\_\_\_\_ -\_\_\_\_\_\_ -\_\_\_\_\_\_
- alpha-synuclein aggregations
- mitochondrial dysfunctions
- pathogenic genetic mutations
- dopamine dysregulation
- calcium channels altered activity
- neuro-inflammation
from ____ to ____ dopaminergic transmission diminished because of ____ as _____
SN to putamen
alpha-synuclein aggregations as Lewy Body
alpha-synuclein aggregation:
- Why does this occur?
- What two misfolded-protein disposal mechanisms malfunction to lead to aggregations?
-HSP function compromised –> chaperone failure and sequestering of HSP –> alpha-synuclein aggregations –> Lewy body pathology of SN –> PD
- 1) (Lysosome system) Mutation in LAMP2A –> alpha-synuclein lysosome formation compromised –> perturbed autophagy –> Lewy body pathology in SN –> PD
- 2) (Ubiquitin-proteosome system) Mutation in UCH-L1 –> E3 Ubiquitin formation stops –> proteosomal system inactivation –> Lewy body pathology in SN –> PD
2 pathways showing how mitochondrial dysfunction leads to PD (draw out if possible)
1) ETC malfunction –> energy failure –> apoptosis –> PD
2) ETC malfunction –> electrons leaked from the membrane –> leads to superoxide radicals (Fenton rxn O2-) –> leading to DNA damage –> mitochondrial damage –> PD AND production of ROS –> oxidative stress –> alpha-synuclein aggregations –> dopaminergic neuron loss –> PD
primary motor symptoms of PD: _____, _____, _____, _____
- Bradykinesia: slowness of a voluntary movement
- Resting tremor: a rhythmic, involuntary oscillatory movement of a body part (limb, hand, or foot)
- Rigidity: increased resistance; stiffness and disturbance
- Postural instability: balance impairments
secondary motor symptoms of PD: 6 total
- gait impairments
- micrographia - handwriting becomes progressively smaller
- speech difficulties
- dysphagia - difficulty swallowing
- dystonia - abnormal tone of any tissue
- impairments of precision grip
non-motor symptoms of PD
neuropsychiatric: ____, ____, ____
depression, cognitive dysfunction, dementia
non-motor symptoms of PD
sleep disorders: ______ and _____
insomnia
rapid eye movement disorders
non-motor symptoms of PD
autonomic symptoms: _____, _____, _____
bladder disorders, orthostatic hypotension, erectile impotence
non-motor symptoms of PD
GI dysfunctions: _____ and _____
dysphagia bowel dysfunctions (slowed colonic transit and constipation)
