Classic and New Animal Models of Parkinson's Disease

Table 1

Model	Behavioral symptoms	Nigrostriatal damage	Synuclein aggregation/Lewy body formation	Uses of the model	Disadvantages
6-OHDA	Rotational behavior after unilateral injection	Loss of DA innervation at injection site (striatum)	No inclusions	Screen therapies that may improve PD symptoms. Study mechanisms of cell death	Requires intracerebral injection, very little synuclein involvement.
MPTP	Motor impairments in primates; Less obvious motor impairments in acute rodent models	Loss of DA neurons dependent on dosing regimen, reaching 95% in acute high-dose conditions.; Reduced DA levels in striatum concurrent with midbrain DA neuron loss	Inclusions not prevalent. Few cases of synuclein aggregation in nonhuman primates, as well as increased synuclein immunoreactivity in rodents.	Screen therapies that may improve PD symptoms. Study mechanisms of cell death	Nonprogressive model of cell death. Inclusiones are rare.
Rotenone	Reports of decreased motor activity in rodents	Loss of DA neurons accompanied by reduced DA innervation in striatum	Synuclein aggregation in DA neurons.	Test neuroprotective compounds	Substantial morbidity and mortality. Labor and time intensive.
Paraquat	No clear motor deficits	Decreased striatal TH immunoreactivity	No inclusions present, but increased synuclein immunoreactivity in DA neurons of the SN	Test neuroprotective strategies	Not extensively tested. Effects in other neurotransmitter systems.
α-synuclein	Severe motor deficits in the A53T model, less in the A30P model	Generally no DA neuron degeneration observed	Synuclein aggregation found in DA neurons, generally restricted to A53T model	Study the role of synuclein aggregation in PD, as well as the normal role of synuclein	Generally no DA neuron death observed with synuclein models
LRRK2	Few behavioral deficits seen in Drosophila mutation models	No effect on DA development or maintenance in knockouts, minimal levels of degeneration in mutation models	Generally not observed	Study the role of LRRK2 mutations related to PD	General lack of degeneration and general lack of synuclein aggregation.