Table 1 Animal models of Parkinson’s disease
Model | α-synuclein pathology | Dopaminergic (TH+) neurodegeneration | Motor deficits | Cognitive/Behavioral deficits | References | |
|---|---|---|---|---|---|---|
Toxin Models of Parkinson’s disease | ||||||
6-OHDA (mice, rats) | Not present | Nigra: Within 12 h of injection, with progressive fiber degeneration during the following 7–10 av days Medial frontal lobe: 3 to 5 weeks post-injection Striatum: 24 h after injections which progress up to 3 weeks | Appears 1 week post injection and severity vary with extension of DA neurodegeneration | Behaviors deficits can appear 2–3 weeks after injection. | [234] | |
MPTP (mice, rats, NHPs) | NHP may develop αsyn inclusions reflective of an early stage of PD at 1-month post-injection | Acute: 12 h in mice Chronically: 3 weeks for degeneration of the nigrostriatal pathway in mice 42 + days in rats 1-month post-injection in monkeys. Mice and NHP are treated systemically. Rats require intra-cranial injection. | Rotarod deficits appear 2 weeks after injection. Rats and mice display mild symptoms. NHPs display parkinsonism-like symptoms. | Increase in anxiety-like behavior and impairment of object recognition in rats. NHP demonstrates impairment across multiple cognitive test 3–5 weeks after administration. | [238] [241] | |
Rotenone (mice, rats) | αsyn accumulation in the SNc present 9 months after rotenone exposure in rats In mice αsyn accumulation occurs two weeks after exposure in the striatum and SNc | Significant loss of dopamine neurons 3 months after rotenone exposure In mice two weeks after exposure experienced substantial loss of dopamine neurons in the SNc after 2 weeks | Acute motor deficits present within 3–5 days after injection. More prevalent motor deficits after 3 months in rats | Behavioral symptoms may occur in rats after 4 months post-exposure in rats. Cognitive deficits can occur in mice 3 weeks after exposure to rotenone Gastrointestinal dysfunction may also be present in rats 4 weeks after exposure. | [245] [246] | |
Non-toxin models of Parkinson’s disease | ||||||
AAV-αsyn (mice, rats, NHPs) | Present– αsyn overproduction and aggregates. LB-like inclusions in NHPs after 4 months. | Rodents: Degeneration of neurons in the nigrostriatal pathway at 3–4 weeks after injection NHP: Degeneration of dopamine neurons takes 4 months in the nigrostriatal pathway Extension of lesion varies according to promotor type, capsid serotype, wild-type αsyn or mutated αsyn, etc. | Motor deficits 7 weeks post-injection in rodent models (staircase, stepping test, and rotarod) Motor deficits appear at 6 months in NHP | Depressive-like phenotype in the swim test 3 weeks post injection. | [249] | |
PFF (mice, rats) | Present– αsyn aggregates and LB-like inclusions in the nigrostriatal pathway, thalamus, and occipital cortex Rats show αsyn accumulation in the nigrostriatal pathway in 2 months, and the amygdala in 6 months post-injection, | Mice: 60 days post-injection in the nigra and 90 days post-injection Rats: Degeneration of dopamine neurons in the nigra occurs 4 to 6 months after injection in rats | Motor deficits are present approximately 60 days post-injection in mice. | Not present. | ||
M83 Transgenic mice (A53T αsyn) | Present after 20 months | Dopamine degeneration in the nigra between 8–16 months of age | Movement is impaired by 8 months of age. | Sensorimotor deficits at 1–2 months Cognitive deficits present at 6 months | ||
Line 61 mice | Present | Present | Present | Present | ||
BAC-LRRK2-R1441G transgenic mice | Not present | Dopamine loss in the SNc occurred at age 9–10 months old | Motor deficits observed at 10–12 months | Not present | [255] [256] | |
BAC-SNCA-A30P transgenic mice | αsyn overproduction at 3 months in the SNc and at 6 months in the STR. | Not present | Mild rearing impairment at 12 months | Not present | [57] [257] | |
BAC-SNCA-OVX transgenic mice | Overproduction in the midbrain at 3 months of age. | Loss of dopamine neurons in the SNc at 18 months of age. | Motor symptoms present at 18 months of age. | Gastrointestinal symptoms are present. | ||
BAC-SNCAA53T/− transgenic mice | Overproduction after one month post injection in the SNc, Striatum, olfactory bulb and cerebral cortex | Acute loss at 1 month post injection Loss of dopamine neurons at 18 months of age | Present at 6 months | Rapid eye movement at 5 months of age. Hyposmia at 9 months of age | ||