Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease

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.

p53, Oxidative Stress, and Aging

“…ROS production and a decreased antioxidant capacity are thought to contribute to the aging process by oxidative modification of different macromolecules, such as lipids, proteins, and genomic DNA (12,20,25,62,63,65,96,109,117).…”

Oxidative Stress in Neurodegenerative Diseases

“…MDA, HNE, or TBARS were enhanced in all of those models in the cerebral cortex or/and hippocampus or/and the whole brain [237][238][239][240][241][247][248][249][250][251][252][253][254][255]. Oxidative modification of proteins has also been demonstrated in the cortex and whole brain homogenate of transgenic AD mice [253,255] and in the cerebral cortex and hippocampus of an Aβ 1-42 mouse model [247].…”

Iron, Oxidative Stress and Health

“…Diseased neurons can remain viable for 10 years or longer and as such must have sufficient protective mechanisms to maintain normal homeostasis. However, at some point in a neurodegenerative disorder, the oxidative insults may overwhelm cellular antioxidant defense systems leading to cellular dysfunction and death (Siedlak, 2009). In fact oxidative stress is regarded as one of the earliest changes in the pathogenesis of AD that may be present several years before the disease overtly manifests itself (Smith et al, 2010).…”