Abstract
Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-β load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AβPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 156-164 |
| Number of pages | 9 |
| Journal | Free Radical Research |
| Volume | 43 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2009 |
| Externally published | Yes |
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Keywords
- Alzheimer's disease
- Amyloid-β
- Antioxidant
- R-alpha lipoic acid
- Transgenic mice
ASJC Scopus subject areas
- Biochemistry
Cite this
Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease. / Siedlak, Sandra L.; Casadesus, Gemma; Webber, Kate M.; Pappolla, Miguel; Atwood, Craig S.; Smith, Mark A.; Perry, George.
In: Free Radical Research, Vol. 43, No. 2, 2009, p. 156-164.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease
AU - Siedlak, Sandra L.
AU - Casadesus, Gemma
AU - Webber, Kate M.
AU - Pappolla, Miguel
AU - Atwood, Craig S.
AU - Smith, Mark A.
AU - Perry, George
PY - 2009
Y1 - 2009
N2 - Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-β load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AβPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit.
AB - Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-β load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AβPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit.
KW - Alzheimer's disease
KW - Amyloid-β
KW - Antioxidant
KW - R-alpha lipoic acid
KW - Transgenic mice
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UR - http://www.scopus.com/inward/citedby.url?scp=60349086658&partnerID=8YFLogxK
U2 - 10.1080/10715760802644694
DO - 10.1080/10715760802644694
M3 - Article
C2 - 19160110
AN - SCOPUS:60349086658
VL - 43
SP - 156
EP - 164
JO - Free Radical Research
JF - Free Radical Research
SN - 1071-5762
IS - 2
ER -