L17 - Parkinsons Flashcards
what is parkinsons
an age related neurodegenerative disease that affects motor symptoms
motor symptoms of PD
- resting tremor
- postural instability
- bradykinesia (slow movement, hesitation movement)
- rigidity - increased resistance to passive limb movement (muscle and joint stiffness)
what are the non motor symptoms of PD
REM sleep disorders autonomic dysfuntion cognitive decline pain anxiety and depression
many more
describe the aetiology of PD
sporadic, late onset
underlying cause unknown
genetic
environmental
describe the genetic influence in PD
~10% of cases have a genetic involvement (associated with mutations in PARK1-10 genes)
what are the PARK1-10 genes involved in?
mitochondrial function / ability lysosomes and proteasomes in brain to breakdown abnormally processed proteins
what is the role of the PARK 1 gene
encodes alpha -synuclein protein, which is over expressed in PD
explain environmental influence of PD
- some toxins (MPTP) can induce PD in humans (addicts believed it was heroin)
- some pesticides can trigger PD in rats
- influence of gut microbiome - a-synuclein aggregates found in GI tract -PD could originate in gut
describe the pathology of PD
- degeneration of pigmented (neuromelanin, and so DA containing) cell bodies in substantia nigra pars compacta
(neuromelanin is a by-product of DA oxidation) - presence of lewy bodies in DAergic neurones (and throughout brain) which contain aggregates of a-synuclein
- reduced DA in DAergic terminals in striatum
what do lewy bodies contain
aggregates of a-synuclein
what is the significant DA pathway in PD
nigrostriatal pathway
from substantia Nigra projecting to striatum (caudate nuclei and putamen)
what pathway is degraded in PD?
nigrostriatal
what contributes to degradation of the nigrostriatal pathway in PD?
- oxidative stress
- faulty protein degradation (a-synuclein aggregation)
- inflammation
- glutamate toxicity
what is the major brain pathway circuit in movement
what NTs are involved
basal ganglia motor circuit
ACh (striatal interneuroens)
DA (nigrostriatal)
GABA (striatal and thalamic pathways)
Glutamate (corticostriatal and thalamocortical pathways)
what are the major ACh pathways in the basal ganglia motor circuit
striatal interneuroens
what are the major DA pathways in the basal ganglia motor circuit
nigrostriatal patwhay
what are the major GABA pathways in the basal ganglia motor circuit
striatal and thalamic pathways
what are the major glutamate pathways in the basal ganglia motor circuit
corticostriatal and thalamocortical pathways
what is the overal main fucntion of the basal ganglia pathway
receive inputs from SNc and striatum
filter this info and send it back via thalamus to cortex which sends signals for movement
this can occur via a direct or indirect pathway