ABSTRACT Previous in vitro studies have shown that walnut extract can inhibit amyloid-β (Aβ) fibr... more ABSTRACT Previous in vitro studies have shown that walnut extract can inhibit amyloid-β (Aβ) fibrillization, can solubilize its fibrils, and has a protective effect against Aβ-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 AD (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.
Abstract. Previous in vitro studies have shown that walnut extract can inhibit amyloid- (A) fibri... more Abstract. Previous in vitro studies have shown that walnut extract can inhibit amyloid- (A) fibrillization, can solubilize its fibrils, and has a protective effect against A-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...
Ó The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Amy... more Ó The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Amyloid beta-protein (Ab) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimer’s disease. Ab 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 Ab, and solubilization of preformed fibrillar Ab by walnut extract was previously reported. The present study was designed to investigate whether walnut extract can protect against Ab-induced oxidative damage and cytotoxicity. The effect of walnut extract on Ab-induced cellular damage, ROS generation and apoptosis in ...
The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), consid... more The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-Carnitine (4-N-trimethylammonium-3-hydroxybutric acid) plays an important role in transport of fatty acid from cytoplasm to mitochondria for energy production. Previous studies in our laboratory reported L-carnitine as a free radical scavenger in aged rats. In the present study we focused the effect of L-carnitine on the activities of electron transport chain in young and aged rats. The activities of electron transport chain complexes were found to be significantly decreased in aged rats when compared to young control rats. Supplementation of carnitine to young and aged rats for 14 and 21 days improved the electron transport chain complexes levels in aged rats when compared with young rats in duration dependent manner. No significant changes were observed in young rats. Our result suggested that L-carnitine improved the activitie...
ABSTRACT Background: Recent studies have suggested increased oxidative stress in autism. Most of ... more ABSTRACT Background: Recent studies have suggested increased oxidative stress in autism. Most of these studies were done with serum, plasma or erythrocyes. The studies with cell cultures are lacking in autism. Under normal conditions, a dynamic equilibrium exists between the production of free radicals (reactive oxygen species -ROS and reactive nitrogen species- RNS) and the anti-oxidant capacity of the cell. The free radicals are highly reactive, and their elevated levels lead to oxidative/ nitrosative stress and cell death. Objectives: The aim was to study the status of oxidative/ nitrosative stress in lymphoblasts from autism by analyzing lipid peroxidation, generation of free radicals (ROS/RNS) and extent of membrane damage. Methods: The lymphoblasts from autistic and control subjects were obtained from Autism Genetic Resources Exchange Program, and the cell lysates were prepared. Lipid peroxidation was assessed by measuring malonyldialdehyde, an end product of fatty acid oxidation. ROS levels (basal and upon induction by Fenton reaction) were determined by using dichlorofluorescin-diacetate (DCFH-DA) as a fluorescent probe. RNS levels were measured by nitric oxide fluorometric assay kit. Damage of the plasma membrane was evaluated by measuring the amount of intracellular lactate dehydrogenase (LDH) that was released into the conditioned medium. Results: Lipid peroxidation was significantly increased in lymphoblasts from autism as compared with control lymphoblasts, suggesting increased oxidative damage in autism. The levels of ROS and RNS were significantly increased in the lymphoblasts from autism as compared with control lymphoblasts, suggesting increased generation of free radicals in autism. LDH leakage was also increased in lymphoblasts of autism as compared with controls, suggesting that membrane integrity is affected in autism. Conclusions: Autism is associated with increased formation of free radicals (ROS and RNS), which leads to increased oxidative damage and membrane damage.
Background: Accumulating evidence suggests that oxidative stress may provide a link between susce... more Background: Accumulating evidence suggests that oxidative stress may provide a link between susceptibility genes and pre- and post-natal environmental risk factors in the pathophysiology of autism. Brain tissue is highly heterogeneous with different functions localized in specific areas, and it is highly vulnerable to oxidative stress due to its limited antioxidant capacity and higher energy requirement. Protein oxidation is defined as the covalent modification of a protein induced either directly by reactive oxygen species (ROS) or indirectly by reaction with secondary by-products of oxidative stress. Protein carbonyl derivatives of amino acids (pro, arg, lys, thr) are the most common products of protein oxidation. Objectives: In this study, the status of protein oxidation was compared in postmortem brain samples from the cerebellum and frontal, temporal, parietal and occipital cortex from autistic subjects with age range of 4 to 39 yrs (N = 7-10 for different brain regions) and ag...
Background: Recent studies have suggested increased oxidative stress in autism. Most of these stu... more Background: Recent studies have suggested increased oxidative stress in autism. Most of these studies were done with serum, plasma or erythrocyes. The studies with cell cultures are lacking in autism. Under normal conditions, a dynamic equilibrium exists between the production of free radicals (reactive oxygen species -ROS and reactive nitrogen species- RNS) and the anti-oxidant capacity of the cell. The free radicals are highly reactive, and their elevated levels lead to oxidative/ nitrosative stress and cell death. Objectives: The aim was to study the status of oxidative/ nitrosative stress in lymphoblasts from autism by analyzing lipid peroxidation, generation of free radicals (ROS/RNS) and extent of membrane damage. Methods: The lymphoblasts from autistic and control subjects were obtained from Autism Genetic Resources Exchange Program, and the cell lysates were prepared. Lipid peroxidation was assessed by measuring malonyldialdehyde, an end product of fatty acid oxidation. ROS ...
International Journal of Developmental Neuroscience, 2005
Oxidative stress has been shown to play a major role in aging and in neurodegenerative disorders.... more Oxidative stress has been shown to play a major role in aging and in neurodegenerative disorders. Protein modification is one of the important consequences of oxidative stress. In the present study, we evaluated the role of grape seed extract on memory, reactive oxygen species production, protein carbonyls (PCO), and thiol status in discrete regions of central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I--control young rats, Group II--young rats treated with grape seed extract (100 mg/kg BW) for 30 days, Group III--aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg BW) for 30 days. Memory loss was observed in the aged rats. Age associated increase in reactive oxygen species production and protein oxidation was observed in the spinal cord; cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). The levels of total thiol, non-protein thiol, protein thiols were found to be significantly decreased in spinal cord and all the brain regions studied in aged rats when compared to young rats. Supplementation of aged rats with grape seed extract showed increased memory performance and declined reactive oxygen species production, decreased protein carbonyl levels and improved thiol levels. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical induced protein oxidation in aged rats thereby protecting the central nervous system from the reactive oxygen species.
Aging is the accumulation of diverse deleterious changes in the cells and tissues leading to incr... more Aging is the accumulation of diverse deleterious changes in the cells and tissues leading to increased risk of diseases. Oxidative stress is considered as a major risk factor and contributes to age related increase in DNA oxidation and DNA protein cross-links in central nervous system during aging. In the present study, we have evaluated the salubrious role of grape seed extract on accumulation of oxidative DNA damage products such as 8-OHdG and DNA protein cross-links in aged rats. Male albino rats of Wistar strain were divided into four groups: Group I, young control rats; Group II, young rats treated with grape seed extract (100 mg/kg b.wt.) for 30 days; Group III, aged control rats; Group IV, aged rats supplemented with grape seed extract (100 mg/kg b.wt.) for 30 days. Our results, thus, revealed that grape seed extract has inhibiting effect on the accumulation of age-related oxidative DNA damages in spinal cord and in various brain regions such as cerebral cortex, striatum and hippocampus.
ABSTRACT Previous in vitro studies have shown that walnut extract can inhibit amyloid-β (Aβ) fibr... more ABSTRACT Previous in vitro studies have shown that walnut extract can inhibit amyloid-β (Aβ) fibrillization, can solubilize its fibrils, and has a protective effect against Aβ-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 AD (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.
Abstract. Previous in vitro studies have shown that walnut extract can inhibit amyloid- (A) fibri... more Abstract. Previous in vitro studies have shown that walnut extract can inhibit amyloid- (A) fibrillization, can solubilize its fibrils, and has a protective effect against A-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...
Ó The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Amy... more Ó The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Amyloid beta-protein (Ab) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimer’s disease. Ab 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 Ab, and solubilization of preformed fibrillar Ab by walnut extract was previously reported. The present study was designed to investigate whether walnut extract can protect against Ab-induced oxidative damage and cytotoxicity. The effect of walnut extract on Ab-induced cellular damage, ROS generation and apoptosis in ...
The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), consid... more The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-Carnitine (4-N-trimethylammonium-3-hydroxybutric acid) plays an important role in transport of fatty acid from cytoplasm to mitochondria for energy production. Previous studies in our laboratory reported L-carnitine as a free radical scavenger in aged rats. In the present study we focused the effect of L-carnitine on the activities of electron transport chain in young and aged rats. The activities of electron transport chain complexes were found to be significantly decreased in aged rats when compared to young control rats. Supplementation of carnitine to young and aged rats for 14 and 21 days improved the electron transport chain complexes levels in aged rats when compared with young rats in duration dependent manner. No significant changes were observed in young rats. Our result suggested that L-carnitine improved the activitie...
ABSTRACT Background: Recent studies have suggested increased oxidative stress in autism. Most of ... more ABSTRACT Background: Recent studies have suggested increased oxidative stress in autism. Most of these studies were done with serum, plasma or erythrocyes. The studies with cell cultures are lacking in autism. Under normal conditions, a dynamic equilibrium exists between the production of free radicals (reactive oxygen species -ROS and reactive nitrogen species- RNS) and the anti-oxidant capacity of the cell. The free radicals are highly reactive, and their elevated levels lead to oxidative/ nitrosative stress and cell death. Objectives: The aim was to study the status of oxidative/ nitrosative stress in lymphoblasts from autism by analyzing lipid peroxidation, generation of free radicals (ROS/RNS) and extent of membrane damage. Methods: The lymphoblasts from autistic and control subjects were obtained from Autism Genetic Resources Exchange Program, and the cell lysates were prepared. Lipid peroxidation was assessed by measuring malonyldialdehyde, an end product of fatty acid oxidation. ROS levels (basal and upon induction by Fenton reaction) were determined by using dichlorofluorescin-diacetate (DCFH-DA) as a fluorescent probe. RNS levels were measured by nitric oxide fluorometric assay kit. Damage of the plasma membrane was evaluated by measuring the amount of intracellular lactate dehydrogenase (LDH) that was released into the conditioned medium. Results: Lipid peroxidation was significantly increased in lymphoblasts from autism as compared with control lymphoblasts, suggesting increased oxidative damage in autism. The levels of ROS and RNS were significantly increased in the lymphoblasts from autism as compared with control lymphoblasts, suggesting increased generation of free radicals in autism. LDH leakage was also increased in lymphoblasts of autism as compared with controls, suggesting that membrane integrity is affected in autism. Conclusions: Autism is associated with increased formation of free radicals (ROS and RNS), which leads to increased oxidative damage and membrane damage.
Background: Accumulating evidence suggests that oxidative stress may provide a link between susce... more Background: Accumulating evidence suggests that oxidative stress may provide a link between susceptibility genes and pre- and post-natal environmental risk factors in the pathophysiology of autism. Brain tissue is highly heterogeneous with different functions localized in specific areas, and it is highly vulnerable to oxidative stress due to its limited antioxidant capacity and higher energy requirement. Protein oxidation is defined as the covalent modification of a protein induced either directly by reactive oxygen species (ROS) or indirectly by reaction with secondary by-products of oxidative stress. Protein carbonyl derivatives of amino acids (pro, arg, lys, thr) are the most common products of protein oxidation. Objectives: In this study, the status of protein oxidation was compared in postmortem brain samples from the cerebellum and frontal, temporal, parietal and occipital cortex from autistic subjects with age range of 4 to 39 yrs (N = 7-10 for different brain regions) and ag...
Background: Recent studies have suggested increased oxidative stress in autism. Most of these stu... more Background: Recent studies have suggested increased oxidative stress in autism. Most of these studies were done with serum, plasma or erythrocyes. The studies with cell cultures are lacking in autism. Under normal conditions, a dynamic equilibrium exists between the production of free radicals (reactive oxygen species -ROS and reactive nitrogen species- RNS) and the anti-oxidant capacity of the cell. The free radicals are highly reactive, and their elevated levels lead to oxidative/ nitrosative stress and cell death. Objectives: The aim was to study the status of oxidative/ nitrosative stress in lymphoblasts from autism by analyzing lipid peroxidation, generation of free radicals (ROS/RNS) and extent of membrane damage. Methods: The lymphoblasts from autistic and control subjects were obtained from Autism Genetic Resources Exchange Program, and the cell lysates were prepared. Lipid peroxidation was assessed by measuring malonyldialdehyde, an end product of fatty acid oxidation. ROS ...
International Journal of Developmental Neuroscience, 2005
Oxidative stress has been shown to play a major role in aging and in neurodegenerative disorders.... more Oxidative stress has been shown to play a major role in aging and in neurodegenerative disorders. Protein modification is one of the important consequences of oxidative stress. In the present study, we evaluated the role of grape seed extract on memory, reactive oxygen species production, protein carbonyls (PCO), and thiol status in discrete regions of central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I--control young rats, Group II--young rats treated with grape seed extract (100 mg/kg BW) for 30 days, Group III--aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg BW) for 30 days. Memory loss was observed in the aged rats. Age associated increase in reactive oxygen species production and protein oxidation was observed in the spinal cord; cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). The levels of total thiol, non-protein thiol, protein thiols were found to be significantly decreased in spinal cord and all the brain regions studied in aged rats when compared to young rats. Supplementation of aged rats with grape seed extract showed increased memory performance and declined reactive oxygen species production, decreased protein carbonyl levels and improved thiol levels. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical induced protein oxidation in aged rats thereby protecting the central nervous system from the reactive oxygen species.
Aging is the accumulation of diverse deleterious changes in the cells and tissues leading to incr... more Aging is the accumulation of diverse deleterious changes in the cells and tissues leading to increased risk of diseases. Oxidative stress is considered as a major risk factor and contributes to age related increase in DNA oxidation and DNA protein cross-links in central nervous system during aging. In the present study, we have evaluated the salubrious role of grape seed extract on accumulation of oxidative DNA damage products such as 8-OHdG and DNA protein cross-links in aged rats. Male albino rats of Wistar strain were divided into four groups: Group I, young control rats; Group II, young rats treated with grape seed extract (100 mg/kg b.wt.) for 30 days; Group III, aged control rats; Group IV, aged rats supplemented with grape seed extract (100 mg/kg b.wt.) for 30 days. Our results, thus, revealed that grape seed extract has inhibiting effect on the accumulation of age-related oxidative DNA damages in spinal cord and in various brain regions such as cerebral cortex, striatum and hippocampus.
Uploads
Papers by Balu Muthaiyah