Oxidative Stress in Genetic Mouse Models of Parkinson’s Disease

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]
DJ-1 KO	3-4	Lesion after MPTP	Striatum	TH WB, DA HPLC	↑	[141]
DJ-1 OExp	N.R.	Lesion after MPTP	SN	TH IHC	↓	[142]
Parkin KO	3	Lesion after 6-OHDA	Striatum	DA HPLC	↔	[98]
		Lesion after METH	Striatum	DA HPLC	↔
Parkin OExp	N.R.	Lesion after MPTP	SN	TH IHC	↓	[142]
PINK1 KO	24	Mitochondrial ROS after paraquat, 6-OHDA, DA, or rotenone	Striatum, cortex	Amplex red assay	↔	[29]
PINK1 KO	6	IL-1β, IL-12, and IL-10 after LPS	Striatum	ELISA	↑	[104]
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]
SNCA KO	2-3	Lesion after MPTP	Striatum	DA HPLC	↓	[146]
SNCA KO	2-3	Lesion after MPTP	Striatum	DA HPLC	↓	[147]
SNCA KO	9	Lesion after MPTP	SN	TH IHC	↓	[148]
SNCA KO	2-3	Lesion after MPTP	SN, striatum	TH IHC, DA HPLC	↓	[149]
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	↔
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]
SNCA OExp A53T	9-10	Lesion after MPTP	Midbrain	DA HPLC	↔	[154]
		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]
	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]
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.