Toxin-Induced and Genetic Animal Models of Parkinson's Disease
Table 1
Representative neurotoxin-induced mammalian models of Parkinson’s disease.
Neurotoxin
Behavioral and pathological features
Molecular mechanisms
MPTP
(1) Parkinsonism (akinesia, rigidity, and tremor) with acute onset (2) Relatively less potent in rodents (3) Good response to L-DOPA and DA-agonists (4) Loss of TH-neurons (-fibers) and DA-content in nigrostriatal region (5) Loss of TH-neurons (-fibers) in ENS (6) α-Synuclein-positive inclusions (7) No typical LBs
(1) Easily crosses the BBB (2) Converted to MPP+ in glial cells (3) Transferred into mitochondria by transporters (4) Inhibits electron transport chain complex I (5) Upregulation of iNOS, NADPH-oxidase, and ROS (6) Microglial activation
6-OHDA
(1) Intracerebral administration (2) Quantifiable locomotor abnormalities (rotation, akinsesia) (3) Good response to L-DOPA and DA-agonists (4) Loss of TH-neurons (-fibers) and DA-content in nigrostriatal region (5) No typical LBs
(1) Transferred into mitochondria by transporters (2) Inhibits electron transport chain complex I (3) Microglial activation
Rotenone
(1) Parkinsonism (bradykinesia, fixed posture, and rigidity) (2) Good response to L-DOPA and DA-agonists (3) Loss of TH-neurons (-fibers) and DA-content in nigrostriatal region (4) α-Synuclein-positive inclusions, resemblance to true LBs (5) Loss of myenteric neurons
(1) Easily crosses the BBB (2) Inhibits electron transport chain complex I (3) Upregulation of NADPH-oxidase (4) Microglial activation
Paraquat (+ Maneb)
(1) Parkinsonism similar to that of induced by MPTP (2) Loss of DA-content in nigrostriatal region (3) α-Synuclein-positive inclusions with long exposure
(1) Crosses the BBB by neutral amino acid transporter (2) Inhibits electron transport chain complex I (3) Reduction of nAchR-mediated DA release (4) Inhibits complex III (Maneb)
