Oxidative Stress in Genetic Mouse Models of Parkinson’s Disease

Table 2

Oxidative stress parameters in transgenic mouse models of Parkinson’s disease.

Model	Age (mo.)	Marker for oxidative stress	Sampled region	Technique	Outcome (versus control)	References
DJ-1 KO	5, 11	Protein oxidation	Entire brain	Oxyblot	↔	[93]
DJ-1 KO	2-3,18–24	Protein oxidation	Entire brain	Oxyblot	↔	[94]
		Mitochondrial ROS	Entire brain	Amplex red assay	↑
		Mitochondrial aconitase activity	Entire brain	Mitochondrial aconitase activity assay	↓ at 2-3 mo., ↔ at 18–24 mo.
DJ-1 KO	24–27	DNA/RNA oxidation	SN	IHC	↔	[95]
		Nitrotyrosine	SN	IHC	↔
		4-HNE	SN	IHC	↔
DJ-1 KO	1	Mitochondrial ROS	SN	2PLSM	↑	[96]
		Mn-SOD	SN	RT-qPCR	↔
		GPx	SN	RT-qPCR	↔
		Catalase	SN	RT-qPCR	↔
DJ-1 KO	4–6	Mitochondrial ROS	Entire brain	PHPA assay	↑	[97]
Parkin KO	22	Protein oxidation	Striatum, cortex	Oxyblot	↔	[98]
Parkin KO	11	Total GSH	Striatum	Method of Tietze	↑	[99]
		GSSH	Striatum	Method of Griffith	↔
Parkin KO	8	Peroxiredoxin 1	Ventral midbrain	2DGE + MS	↓	[100]
		Peroxiredoxin 2	Ventral midbrain	2DGE + MS	↓
		Peroxiredoxin 6	Ventral midbrain	2DGE + MS	↓
		Lactoylglutathione lyase	Ventral midbrain	2DGE + MS	↓
	3, 6, 18	4-HNE	Brain	IHC	↔ at 3 or 6 mo., ↑ at 18 mo.
	5–12	Total antioxidant capacity	Serum	Serum antioxidant capacity assay	↓
	3, 18–20	Protein oxidation	Entire brain	Oxyblot	↔ at 3 mo., ↑ at 18–20 mo.
Parkin KO	2, 12	Mitochondrial aconitase	Striatum, cortex	2DGE + MS	↑ in cortex at 2 mo.	[101]
		GSH S-transferase P 2	Striatum, cortex	2DGE + MS	↓ in striatum and cortex at 2 mo.
		Carbonyl reductase [NADPH] 1	Striatum, cortex	2DGE + MS	↑ in striatum at 2 mo.
		Lactoylglutathione lyase	Striatum, cortex	2DGE + MS	↑ in striatum at 2 mo.
		Thioredoxin reductase	Striatum, cortex	2DGE + MS	↑ in striatum at 2 mo.
		Protein oxidation	Striatum, cortex	Oxyblot	↔
Parkin KO	2, 24	Total GSH	Striatum, midbrain, limbic system	Method of Tietze	↑ at 2 mo., ↓ at 24 mo.	[102]
		GSH reductase activity	Striatum, midbrain, limbic system	GSH reductase activity assay	↔ (within KO group, ↑ at 24 mo. versus 2 mo.)
		GPx activity	Striatum, midbrain, limbic system	Method of Flohe and Gunzler	↔ (within KO group, ↑ at 24 mo. versus 2 mo.)
		Catalase activity	Striatum, midbrain, limbic system	Reaction with methanol in presence of H2O2	↔
Parkin KO	19–21	Nitrotyrosine	SN	ELISA	↑	[103]
		Nitrated α-synuclein	SN	IHC	Only KO stain positive
PINK1 KO	3-4	Lipid peroxidation	Striatum, cortex	TBARS levels	↔	[29]
	24	Protein oxidation	Striatum	Oxyblot	↔
		4-HNE	SN	IHC	↔
		Mitochondrial ROS	Striatum, cortex	Amplex red assay	↔
	22–24	Mn-SOD	Striatum	WB	↔
		CuZn-SOD	Striatum	WB	↔
		Catalase	Striatum	WB	↔
		G6-PDH	Striatum	WB	↔
PINK1 KO	2	Mitochondrial ROS		DCF assay	↔	[104]
PINK1 KO	4	GSH synthetase	Striatum, midbrain, cortex	2DGE + MS	↑ in cortex and striatum	[28]
		Peroxiredoxin 1	Striatum, midbrain, cortex	2DGE + MS	↑ in cortex
		Protein oxidation	Striatum, midbrain, cortex	Oxyblot	↔
PINK1 KO	2-3	4-HAE	Left ventricle	MDA/4-HAE kit	↑	[105]
		8-OHdG	Left ventricle	8-OHdG kit	↑
		GSH/GSSG	Left ventricle	GSH/GSSG kit	↓
		SOD activity	Left ventricle	SOD activity kit	↓
		Aconitase activity	Left ventricle	Aconitase activity kit	↓
SNCA KO	N.R.	Hydroxyl radicals	Striatum	4-HBA trapping	↔	[106]
SNCA OExp; A30P	N.R.	Oxidized/nitrated α-syn	Brain	IHC	Only OExp stain positive	[107]
SNCA OExp; A30P	6–14	Protein oxidation	Entire brain	2DGE + WB	↑ (oxidized mitochondrial proteins Car2, Eno1, Ldh2)	[108]
SNCA OExp; A53T	12	Oxidized α-syn	Spinal cord, locus coeruleus	IHC	OExp stain positive	[109]
		Nitrated α-syn	Pons	IHC	OExp stain positive
SNCA OExp; A53T	N.R.	Mitochondrial DNA damage	Brainstem, neocortex, spinal cord	TUNEL technique	↑	[110]
		Nitrated α-syn	Spinal cord	IHC	OExp stain positive
SNCA OExp; A53T A30P	3, 6	GPx 3	Striatum	Microarray	↓	[111]
		SOD 2	Striatum	Microarray	↓
SNCA OExp; WT	12	Oxidized α-syn	Entire brain	WB	↑	[112]

Abbreviations: 2DGE: 2D gelelectrophoresis, 2-HBA: salicylate, 4-HNE: 4-hydroxynonenal, 4-HAE: 4-hydroxyalkenal, 8-OhdG: 8-hydroxydeoxyguanosine, α-syn: α-synuclein, GPx: GSH peroxidase, GSH: glutathion, GSSH: oxidized glutathion, H₂O₂: hydrogen peroxide, IHC: immunohistochemistry, IF: immunofluorescence, KO: knockout, mo: months, MS: mass spectrometry, OExp: overexpression, PHPA: p-hydroxyphenylacetate, ROS: reactive oxygen species, SN: substantia nigra, SOD: sodium dismutase, WB: Western blot, WT: wildtype, ↑: increased, ↓: decreased, ↔: not different.