Table 3.
Gene-environment interactions in transgenic mouse models of Parkinson's disease.
| Model | Age (mo.) | Marker for susceptibility to oxidative stress | Sampled region | Technique | Outcome (versus control) | References |
|---|---|---|---|---|---|---|
| DJ-1 KO | 2-3 | Lesion after MPTP | SN, striatum | TH/DAT IHC, DA HPLC | ↑ | [140] |
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| DJ-1 KO | 3-4 | Lesion after MPTP | Striatum | TH WB, DA HPLC | ↑ | [141] |
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| DJ-1 OExp | N.R. | Lesion after MPTP | SN | TH IHC | ↓ | [142] |
|
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| Parkin KO | 3 | Lesion after 6-OHDA | Striatum | DA HPLC | ↔ | [98] |
| Lesion after METH | Striatum | DA HPLC | ↔ | |||
|
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| Parkin OExp | N.R. | Lesion after MPTP | SN | TH IHC | ↓ | [142] |
|
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| PINK1 KO | 24 | Mitochondrial ROS after paraquat, 6-OHDA, DA, or rotenone | Striatum, cortex | Amplex red assay | ↔ | [29] |
|
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| PINK1 KO | 6 | IL-1β, IL-12, and IL-10 after LPS | Striatum | ELISA | ↑ | [104] |
|
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| PINK1 KD | 20 | Lesion after paraquat | SN, striatum | TH IHC, DA HPLC | ↑ | [143] |
|
| ||||||
| PINK1 OExp | 2-3 | Lesion after MPTP | SN | TH IHC | ↓ | [144] |
|
| ||||||
| SNCA KO | 2 | Lesion after MPTP | SN, striatum | TH IHC | ↓ | [145] |
|
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| SNCA KO | 2-3 | Lesion after MPTP | Striatum | DA HPLC | ↓ | [146] |
|
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| SNCA KO | 2-3 | Lesion after MPTP | Striatum | DA HPLC | ↓ | [147] |
|
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| SNCA KO | 9 | Lesion after MPTP | SN | TH IHC | ↓ | [148] |
|
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| SNCA KO | 2-3 | Lesion after MPTP | SN, striatum | TH IHC, DA HPLC | ↓ | [149] |
|
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| SNCA KO | N.R. | Lesion after MPTP | SN, striatum | DAT IHC, DA HPLC | ↓ | [106] |
| Hydroxyl radicals after 3-NP | Striatum | 4-HBA trapping | ↓ | |||
|
| ||||||
| SNCA KO | 2-3 | Lesion after 6-OHDA | SN | TH IHC | ↓ | [150] |
| Lesion after 6-OHDA | Striatum | DA HPLC | ↔ | |||
|
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| SNCA OExp A30P | 6 | Lesion after MPTP | SN, striatum | TH IHC, DA HPLC | ↔ | [151] |
|
| ||||||
| SNCA OExp A30P | 3-4, 6–8 | Lesion after MPTP | SN | TH IHC | ↑ | [152] |
| Lesion after MPTP | Striatum | DA HPLC | ↔ at 3-4 mo., ↑ at 6–8 mo. | |||
| Lesion after rotenone | SN, striatum | TH IHC, DA HPLC | ↔ | |||
|
| ||||||
| SNCA OExp A53T | 2 | Lesion after MPTP | SN, striatum | TH IHC, DA HPLC | ↔ | [153] |
|
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| SNCA OExp A53T | 9-10 | Lesion after MPTP | Midbrain | DA HPLC | ↔ | [154] |
|
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| 3-NT after MPTP | Olfactory bulb | WB | ↑ | |||
|
| ||||||
| SNCA OExp A53T | 2, 12, 23 | Lesion after iron and/or paraquat | SN | TH IHC | ↔ at 2 mo. and 12 mo., ↑ at 23 mo. | [155] |
|
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| 2, 23 | 3-NT after iron and/or paraquat | SN | TH 3NT IF | ↔ at 2 mo., ↑ at 23 mo. | ||
| 12 | Nitrated α-syn after iron and/or paraquat | SN | TH nSYN IF | ↑ | ||
|
| ||||||
| SNCA OExp A53T | 7 | Lesion after LPS | SN, striatum | TH IHC | ↑ | [156] |
| Nitrated α-syn after LPS | Midbrain | WB | OExp are positive for nitrated α-syn only after LPS | |||
|
| ||||||
| SNCA OExp WT or A53T | 3-4 | Lesion after paraquat | SN | TH IHC | ↓ | [141] |
|
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| SNCA OExp WT | 3-4 | Lesion after paraquat | SN | TH IHC | ↔ | [157] |
|
| ||||||
| SNCA OExp A53T A30P | 2-3 | Lesion after MPTP | Striatum | DAT IHC | ↑ | [158] |
|
| ||||||
| SNCA OExp A53T A30P | 6-7 | Lesion after paraquat+maneb | SN, striatum | TH IHC, DA HPLC | ↑ | [159] |
Abbreviations: 2-HBA: salicylate, 3NT: 3-nitrotyrosine, 6-OHDA: 6-hydroxydopamine, α-syn: α-synuclein, DA: dopamine, DAT: dopamine transporter, HPLC: High Pressure Liquid Chromatography, IHC: immunohistochemistry, IF: immunofluorescence, KO: knockout, KD: knockdown, LPS: lipopolysaccharide, METH: methamphetamine, mo: months, MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, OExp: overexpression, ROS: reactive oxygen species, SN: substantia nigra, TH: tyrosine hydroxylase, WB: Western blot, WT: wildtype, ↑: increased, ↓: decreased, ↔: not different.