ECON 546 Lecture Notes - Lecture 13: Autophagy, Base Pair, Punding
27 Jun 2018
School
Department
Course
Professor
Lecture 13: Parkinsonâs Disease Wednesday, February 21, 2018
Dr. Tak Pan Wong
Epidemiology
- DSM-V: neurocognitive disorders due to PD
- Incidence of about 125/100 000 in Canada
- 1% over age 65, 5% over age 85
- Average age of onset is 61 +/- 10 years
- Occurs more frequently in men (67%)
- Probably a long chronic process underlying the neurodegeneration aspect of the disease
Symptoms
- Rest tremor ď gone when a person voluntarily moves
- Muscle rigidity
- Bradykinesia (slowness of movement)
- Akinesia (difficulty initiating movement)
- Inability to control facial expressions
- Balance impairment
- Abnormal gait
- Problems with speech production, swallowing, and constipation
Pathological Hallmarks
- Degeneration of DA neurons in the substantia nigra pars compacta
oNigrostriatal DA pathway
oSevere loss (70-80%) of DA neurons (dark colour came from neuromelanin)
oThe degree of DA loss correlates with the severity of akinesia and bradykinesia
- There is reduced dark coloration in the substantia nigra ď due to the loss of melanin
pigment in SN cells
- Lewy bodies
oProtein-containing inclusions in the cytoplasm
oLewy bodies are also found in other diseases and in 10% of the elderly
oContains many free and ubiquinated proteins: neurofilaments, parkin,
proteasomal elements and alpha-synuclein
oAccumulation of insoluble proteins in Lewy bodies may be caused by aggregating
poorly degraded and abnormal protein in the cytoplasm
oMight be a defense mechanism ď to try and aggregate all the toxic proteins to
stop them from freeflowing in the brain
Basal Ganglia
- Includes the striatum (nucleus + putamen), globus pallidus (internal and external),
subthalamic nucleus, and substantia nigra (SNc)
- SNc sends massive dopaminergic inputs to the striatum: ventrolateral portion of the SNc
projects to the putamen, and the dorsomedial portion of the SNc projects to the
caudate
find more resources at oneclass.com
find more resources at oneclass.com
oSNc also sends collateral inputs to the globus pallidus and STN
Striatum
- 90% of neurons are projecting medium spiny GABAergic neurons
- Spines receive glutamatergic inputs from multiple cortical regions
- DA inputs terminate on the neck of dendritic spines to modulate excitability and
responsiveness of spiny neurons
Direct and Indirect Pathways
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
1% over age 65, 5% over age 85. Average age of onset is 61 +/- 10 years. Probably a long chronic process underlying the neurodegeneration aspect of the disease. Rest tremor gone when a person voluntarily moves. Degeneration of da neurons in the substantia nigra pars compacta: nigrostriatal da pathway, severe loss (70-80%) of da neurons (dark colour came from neuromelanin, the degree of da loss correlates with the severity of akinesia and bradykinesia. There is reduced dark coloration in the substantia nigra due to the loss of melanin pigment in sn cells. Includes the striatum (nucleus + putamen), globus pallidus (internal and external), subthalamic nucleus, and substantia nigra (snc) 90% of neurons are projecting medium spiny gabaergic neurons. Spines receive glutamatergic inputs from multiple cortical regions. Da inputs terminate on the neck of dendritic spines to modulate excitability and responsiveness of spiny neurons. Neuronal activities along the direct and indirect pathways.
