摘要
BACKGROUND： Prophylactic dietary restriction （DR）, whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents. However, whether the anti-aging and neuroprotective efficacy of DR initiate late in life or accompany the aging process remains unclear.OBJECTIVE： The present study sought to： （1） determine if DR could protect against behavioral decline in mice when implemented during the aging process induced by D-galactose and （2） examine neuronal apoptosis in these aged brains and whether DR could block apoptosis.DESIGN, TIME AND SETTING： The randomized controlled animal study. The experiment was performed at the Experimental Animal Center of Capital Medical University and the Laboratory Center of School of Public Health of Captial Medical University of China from April 2006 to October 2007.MATERIALS： D-galactose （D-gal） was purchased from Beijing Chemical-Regent Company （Beijing, China）. Terminal transferase dUTP nick end labeling （TUNEL） detection kit was obtained from Roche, Germany. Assay kits for antioxidant enzyme activities and malondialdehyde contents were purchased from Jiancheng Institute of Biotechnology （Nanjing, China）. Morris water maze （Friends Honesty Life Sciences Co. Ltd., Hong Kong, China） and Flow Cytometry （Coulter, USA） were used in this study.METHODS： A total of 40 male Institute of Cancer Research （lCR） mice, 3 months old, were equally and randomly divided into D-gal treatment, DR treatment, D-gal ＋ DR treatment and normal control groups, and were then randomly assigned to one of two feeding regimens： ad libitum access to food or DR which received a 70% amount of daily food intake as that by ad libitum fed mice. There were two replicates per feeding regimen and mice were fed for 10 weeks,with or without a daily subcutaneous injection of D-gal at 100 mg/kg.MAIN OUTCOME MEASURES： Animals＇ spatial learning and memory performance were tested in the Morris water maze. Neuronal apoptosis rates were evaluated by Annexin V/flow cytometry assay and TUNEL assay. Lipid peroxidation levels and antioxidant defense capacity of the brain were measured using testing kits.RESULTS： DR markedly reduced the prolonged escape latency of D-gal mice in the water maze test （P〈0.01）. Annexin V and TUNEL assays showed that the D-gal mice had a significant higher percentage of neuronal apoptosis compared with normal control mice （P〈0.05）, and that DR treatment markedly decreased this apoptotic cell death （P〈0.05）. DR also reversed the decline of total superoxide dismutase and glutathione peroxidase activities and the increase of malondialdehyde levels in the brain of D-gal mice （P〈0.05, respectively）.CONCLUSION： DR reduces the impact of D-gal-induced brain aging in mice and can reverse performance decline and neurobiochemical impairments. These results demonstrate that implementation of DR in conditions of chronic oxidative stress can be neuroprotective, and that senium DR can be beneficial for healthy aging.
BACKGROUND： Prophylactic dietary restriction （DR）, whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents. However, whether the anti-aging and neuroprotective efficacy of DR initiate late in life or accompany the aging process remains unclear.OBJECTIVE： The present study sought to： （1） determine if DR could protect against behavioral decline in mice when implemented during the aging process induced by D-galactose and （2） examine neuronal apoptosis in these aged brains and whether DR could block apoptosis.DESIGN, TIME AND SETTING： The randomized controlled animal study. The experiment was performed at the Experimental Animal Center of Capital Medical University and the Laboratory Center of School of Public Health of Captial Medical University of China from April 2006 to October 2007.MATERIALS： D-galactose （D-gal） was purchased from Beijing Chemical-Regent Company （Beijing, China）. Terminal transferase dUTP nick end labeling （TUNEL） detection kit was obtained from Roche, Germany. Assay kits for antioxidant enzyme activities and malondialdehyde contents were purchased from Jiancheng Institute of Biotechnology （Nanjing, China）. Morris water maze （Friends Honesty Life Sciences Co. Ltd., Hong Kong, China） and Flow Cytometry （Coulter, USA） were used in this study.METHODS： A total of 40 male Institute of Cancer Research （lCR） mice, 3 months old, were equally and randomly divided into D-gal treatment, DR treatment, D-gal ＋ DR treatment and normal control groups, and were then randomly assigned to one of two feeding regimens： ad libitum access to food or DR which received a 70% amount of daily food intake as that by ad libitum fed mice. There were two replicates per feeding regimen and mice were fed for 10 weeks,with or without a daily subcutaneous injection of D-gal at 100 mg/kg.MAIN OUTCOME MEASURES： Animals＇ spatial learning and memory performance were tested in the Morris water maze. Neuronal apoptosis rates were evaluated by Annexin V/flow cytometry assay and TUNEL assay. Lipid peroxidation levels and antioxidant defense capacity of the brain were measured using testing kits.RESULTS： DR markedly reduced the prolonged escape latency of D-gal mice in the water maze test （P〈0.01）. Annexin V and TUNEL assays showed that the D-gal mice had a significant higher percentage of neuronal apoptosis compared with normal control mice （P〈0.05）, and that DR treatment markedly decreased this apoptotic cell death （P〈0.05）. DR also reversed the decline of total superoxide dismutase and glutathione peroxidase activities and the increase of malondialdehyde levels in the brain of D-gal mice （P〈0.05, respectively）.CONCLUSION： DR reduces the impact of D-gal-induced brain aging in mice and can reverse performance decline and neurobiochemical impairments. These results demonstrate that implementation of DR in conditions of chronic oxidative stress can be neuroprotective, and that senium DR can be beneficial for healthy aging.
基金
the Beijing Natural Science Foundation,No. 7052008
