ABSTRACT
Previous in vitro studies have shown that walnut extract can inhibit amyloid-ß (Aß) fibrillization, can solubilize its fibrils, and has a protective effect against Aß-induced oxidative stress and cellular death. In this study, we analyzed the effect of dietary supplementation with walnuts on learning skills, memory, anxiety, locomotor activity, and motor coordination in the Tg2576 transgenic (tg) mouse model of Alzheimer's disease (AD-tg). From the age of 4 months, the experimental groups of AD-tg mice were fed custom-mixed diets containing 6% walnuts (T6) or 9% walnuts (T9), i.e., equivalent to 1 or 1.5 oz, respectively, of walnuts per day in humans. The control groups, i.e., AD-tg and wild-type mice, were fed a diet without walnuts (T0, Wt). These experimental and control mice were examined at the ages of 13-14 months by Morris water maze (for spatial memory and learning ability), T maze (for position discrimination learning ability), rotarod (for psychomotor coordination), and elevated plus maze (for anxiety-related behavior). AD-tg mice on the control diet (T0) showed memory deficit, anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability, and motor coordination compared to the Wt mice on the same diet. The AD-tg mice receiving the diets with 6% or 9% walnuts (T6 and T9) showed a significant improvement in memory, learning ability, anxiety, and motor development compared to the AD-tg mice on the control diet (T0). There was no statistically significant difference in behavioral performance between the T6/T9 mice on walnuts-enriched diets and the Wt group on the control diet. These findings suggest that dietary supplementation with walnuts may have a beneficial effect in reducing the risk, delaying the onset, or slowing the progression of, or preventing AD.
Subject(s)
Alzheimer Disease/diet therapy , Juglans , Learning Disabilities/diet therapy , Memory Disorders/diet therapy , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Anxiety/diet therapy , Anxiety/physiopathology , Body Weight , Disease Models, Animal , Female , Learning Disabilities/physiopathology , Maze Learning , Memory Disorders/physiopathology , Mice, Transgenic , Rotarod Performance TestABSTRACT
Amyloid beta-protein (Aß) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimer's disease. Aß is known to increase free radical production in neuronal cells, leading to oxidative stress and cell death. Recently, considerable attention has been focused on dietary antioxidants that are able to scavenge reactive oxygen species (ROS), thereby offering protection against oxidative stress. Walnuts are rich in components that have anti-oxidant and anti-inflammatory properties. The inhibition of in vitro fibrillization of synthetic Aß, and solubilization of preformed fibrillar Aß by walnut extract was previously reported. The present study was designed to investigate whether walnut extract can protect against Aß-induced oxidative damage and cytotoxicity. The effect of walnut extract on Aß-induced cellular damage, ROS generation and apoptosis in PC12 pheochromocytoma cells was studied. Walnut extract reduced Aß-mediated cell death assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction, and release of lactate dehydrogenase (membrane damage), DNA damage (apoptosis) and generation of ROS in a concentration-dependent manner. These results suggest that walnut extract can counteract Aß-induced oxidative stress and associated cell death.
Subject(s)
Antioxidants/pharmacology , Cell Death/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Amyloid beta-Peptides , Animals , Apoptosis/drug effects , Juglans/chemistry , PC12 Cells , RatsABSTRACT
Neuronal dysfunctions in several neurodegenerative diseases such as Down syndrome (DS) have been linked to oxidative stress. In this study, we observed that lipid peroxidation, a marker of oxidative stress, is significantly increased in the frontal cortex of brains of individuals with DS as compared with control subjects. We report here that gelsolin levels are increased in the frontal cortex of individuals with DS as compared with controls during early developmental ages (5 to 13 y). Interestingly, the levels of gelsolin in the frontal cortex were increased as a function of age in both DS and control subjects. Because cytoplasmic gelsolin has 5 free thiol groups (cysteine), and its levels are increased in response to oxidative stress, we propose that gelsolin may serve as an antioxidant protein.
