From Drugs of Abuse to Parkinsonism: The MPTP Mouse Model of Parkinson’s Disease - Drugs of Abuse: Neurological Reviews and Protocols - page 103

Table 1
Major Clinical and Neuropathological Features of Human PD

Major types of symptomatology Characteristic features in human PD

Motor defi cits Rigidity, bradykinesia, resting tremor, gait

disturbance

Progressive nigral cell death Gradual loss of TH-immunoreactive,

dopaminergic neurons in the substantia

nigra pars compacta

Depletion of DA transmission Reduced level of striatal terminal DA, its

metabolites and uptake transporter;

clinically responsive to DA prodrug,

L -DOPA

Detection of postmortem Lewy bodies Concentric, intracytoplasmic inclusion

bodies with a dense core, a peripheral

halo, and radiating neurofi laments;

immunoreactive to proteins such as

-synuclein and ubiquitin, and

contains lipids

model should exhibit as many of the phenotypic features of the disease as
possible. These features should include (1) persistent depletion of close to
80% of the striatal DA and its metabolites, (2) pronounced reduction of striatal
sites for DA uptake, (3) signifi cant (near 50%) loss of substantia nigral cells,
(4) marked defi cit in the animal's motor performance, and (5) formation and
accumulation of inclusion bodies in nigral neurons.
There are several existing experimental models of PD, which have been
developed and characterized for specifi c purposes and used in studies that
examine certain symptomatology of PD or for determining the underlying
mechanisms. These models include the unilateral 6-hydroxydopamine lesion
rat produced by the chemical-induced degeneration of DA neurons (19 , 20)
and Parkinsonism induced pharmacologically either by depleting the stored
DA from nerve terminals (e.g., reserpine) or by blocking the postsynaptic DA
receptors using neuroleptic drugs (e.g., haloperidol, phenothiazines) (21) . Other
models have been reported by using insecticides/pesticides (e.g., rotenone)
(22 , 23) or herbicides (e.g., paraquat) (24 , 25) . Transgenic models have also
been generated in the fruit fl y, Drosophila melanogaster (26) , and the mouse
(27) . These transgenic models overexpress human

-synuclein, a constituent

of Lewy bodies.
As mentioned earlier, MPTP neurotoxicity in humans is irreversible and
the resulting clinical and biochemical profi les closely resemble those of the