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Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease.
Neuroscience 2016; 333:345-55N

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD.

Authors+Show Affiliations

Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang, Guangdong, China.Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang, Guangdong, China; Guangdong Key laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang, Guangdong, China; Guangdong Key laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang, Guangdong, China.Department of Pharmacology, Guangdong Medical College, Zhanjiang, Guangdong 524023, China.Department of Pharmacology, Guangdong Medical College, Zhanjiang, Guangdong 524023, China.Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang, Guangdong, China; Department of Pharmacology, Guangdong Medical College, Zhanjiang, Guangdong 524023, China.The Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Boston 02114, USA.Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang, Guangdong, China; Guangdong Key laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China. Electronic address: lwd@gdlami.com.Guangdong Key laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China. Electronic address: labking@sohu.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27474225

Citation

Wu, Kefeng, et al. "Enriched Endogenous N-3 Polyunsaturated Fatty Acids Alleviate Cognitive and Behavioral Deficits in a Mice Model of Alzheimer's Disease." Neuroscience, vol. 333, 2016, pp. 345-55.
Wu K, Gao X, Shi B, et al. Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease. Neuroscience. 2016;333:345-55.
Wu, K., Gao, X., Shi, B., Chen, S., Zhou, X., Li, Z., ... Huang, R. (2016). Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease. Neuroscience, 333, pp. 345-55. doi:10.1016/j.neuroscience.2016.07.038.
Wu K, et al. Enriched Endogenous N-3 Polyunsaturated Fatty Acids Alleviate Cognitive and Behavioral Deficits in a Mice Model of Alzheimer's Disease. Neuroscience. 2016 10 1;333:345-55. PubMed PMID: 27474225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease. AU - Wu,Kefeng, AU - Gao,Xiang, AU - Shi,Baoyan, AU - Chen,Shiyu, AU - Zhou,Xin, AU - Li,Zhidong, AU - Gan,Yuhong, AU - Cui,Liao, AU - Kang,Jing Xuan, AU - Li,Wende, AU - Huang,Ren, Y1 - 2016/07/27/ PY - 2016/04/09/received PY - 2016/07/21/revised PY - 2016/07/21/accepted PY - 2016/7/31/entrez PY - 2016/7/31/pubmed PY - 2017/9/7/medline KW - Alzheimer’s disease KW - amyloid precursor protein KW - polyunsaturated fatty acids SP - 345 EP - 55 JF - Neuroscience JO - Neuroscience VL - 333 N2 - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/27474225/Enriched_endogenous_n_3_polyunsaturated_fatty_acids_alleviate_cognitive_and_behavioral_deficits_in_a_mice_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(16)30343-8 DB - PRIME DP - Unbound Medicine ER -