Long-Term Dietary Alpha-Linolenic Acid Supplement Alleviates Cognitive Impairment Correlate with Activating Hippocampal CREB Signaling in Natural Aging Rats.
Alpha-linolenic acid (ALA) is a major precursor of the essential n-3 polyunsaturated fatty acid (PUFA), whose deficiency alters the structure and function of membranes and induces cerebral dysfunctions. The major purpose of this study was to investigate the protective effect of prolonged ALA intake on cognitive function during natural aging. Female Sprague-Dawley rats aged 6 months were chronically treated with ALA and/or lard per day for 12 months. Regular diet-treated rats, both young and old (4 and 18 months old, respectively) served as controls. Rats fed on regular diet during aging showed memory deficits in Morris water maze, which were further exacerbated by lard intake. However, supplementation with ALA for 12 months dose-dependently improved the performance in spatial working memory tasks. Memory performance correlated well with the activation of cAMP response element-binding protein (CREB) and increases in both levels of brain-derived neurotrophic factor (BDNF) and its specific receptor tyrosine kinase B (TrkB) phosphorylation in the hippocampus. Further study identified that hippocampal extracellular signal-related kinase (ERK) and Akt rather than calcium calmodulin kinase IV (CaMKIV) and protein kinase A (PKA), the upstream signalings of CREB, were also activated by ALA supplement. Moreover, memory improvement was accompanied with alterations of hippocampal synaptic structure and number, suggestive of enhancement in synaptic plasticity. Together, these results suggest that long-term dietary intake of ALA enhances CREB/BDNF/TrkB pathway through the activation of ERK and Akt signalings in hippocampus, which contributes to its ameliorative effects on cognitive deficits in natural aging.
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.|MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Hui
H
Gao
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.|MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Peipei
P
Yan
MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Shun
S
Zhang
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.|MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Hao
H
Huang
Department of Product Processing and Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China.|Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China.
Fenghong
F
Huang
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.|MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Taoping
T
Sun
Department of Product Processing and Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China.|Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China.
Qianchun
Q
Deng
Department of Product Processing and Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China.|Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China.
Qingde
Q
Huang
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.|MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Sijing
S
Chen
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Keqiang
K
Ye
Department of Product Processing and Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China. xujiqu@caas.cn.|Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, People's Republic of China. xujiqu@caas.cn.
Jiqu
J
Xu
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. lgliu@mails.tjmu.edu.cn.|MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. lgliu@mails.tjmu.edu.cn.
Liegang
L
Liu
D000375:Aging / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D060825:Cognitive Dysfunction / Q000178:diet therapy* / Q000378:metabolism* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019587:Dietary Supplements; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017962:alpha-Linolenic Acid / Q000008:administration & dosage*
D017362:Cyclic AMP Response Element-Binding Protein; D017962:alpha-Linolenic Acid
ALA; Aging; CREB/BDNF/TrkB; Cognition