Animal Models of Parkinson's Disease Flashcards
State the primary quartet of symptoms in PD
Bradykinesia, resting tremor, rigidity, loss of postural reflexes
State some symptoms of autonomic dysfunction
Constipation, postural hypotension, urinary frequency and urgency, impotence, increased sweating
State some symptoms of PD other than the primary quartet
Depression, pain, taste disturbances, anosmia, cognitive decline and dementia, hallucinations, anxiety, confusion, sleep disturbances, autonomic dysfunction
Do animals naturally develop PD?
No
How many more nigrostriatal connections are there in the human brain than the mouse brain?
150,000
Why might human nigrostriatal connections be more vulnerable than mouse migrostriatal connections?
Many more connections, greater ATP requirement, more mitochondrial activity, more alpha-synuclein mediated neurotransmission
Name the 2 main types of animal model
Toxin-treated, genetically-altered
Name 3 toxin-treated animal models of PD
6-hydroxydopamine (6-OHDA), MPTP, lactacysteine
Summarise the features of the 6-hydroxydopamine model
Mitochondrial inhibition, selective neuronal loss, iron accumulation causing oxidative stress. No altered proteins
Summarise the features of the MPTP model
Mitochondrial inhibition, selective neuronal loss, iron accumulation causing oxidative stress. May cause altered protein formation and deposition if co-administered with probenecid
Summarise the features of the lactacystin model
Selective neuronal loss, iron accumulation causing oxidative stress, altered protein formation and deposition
Name 4 toxins known to cause parkinsonism in humans
MPTP, manganese, carbon disulphide, cycad seeds
Describe the features of manganese-induced parkinsonism
Fixed gaze, bradykinesia, postural difficulties, rigidity, dystonia
Describe how 6-OHDA is administered to rodent models
Stereotactic injection into the medial forebrain (loss of cells over 7-9 days) or striatum (slower loss) unilaterally into anaesthetised animals
Why is 6-OHDA not used to create a bilateral lesion?
Bilaterally lesioned animals have difficulty eating
Why is 6-OHDA not injected directly into the substantia nigra?
The dopaminergic neuron loss occurs too rapidly to adequately mimic PD
State the 4 ways in which animal models must be valid
Construct validity, face validity, aetiological validity, predictive validity
What is 6-OHDA?
An unstable oxidative by-product of dopamine
Name a way of assessing motor asymmetry in the 6-OHDA rodent model
Amphetamine-induced rotational assessment
Name 2 animals which MPTP can be used in
Non-human primates, C57black mouse