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Endogenous Omega (n)-3 Fatty Acids in Fat-1 Mice Attenuated Depression-Like Behavior, Imbalance between Microglial M1 and M2 Phenotypes, and Dysfunction of Neurotrophins Induced by Lipopolysaccharide Administration.
Nutrients 2018; 10(10)N

Abstract

n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve depression. However, PUFA purities, caloric content, and ratios in different diets may affect the results. By using Fat-1 mice which convert n-6 to n-3 PUFAs in the brain, this study further evaluated anti-depressant mechanisms of n-3 PUFAs in a lipopolysaccharide (LPS)-induced model. Adult male Fat-1 and wild-type (WT) mice were fed soybean oil diet for 8 weeks. Depression-like behaviors were measured 24 h after saline or LPS central administration. In WT littermates, LPS reduced sucrose intake, but increased immobility in forced-swimming and tail suspension tests. Microglial M1 phenotype CD11b expression and concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-17 were elevated, while M2 phenotype-related IL-4, IL-10, and transforming growth factor (TGF)-β1 were decreased. LPS also reduced the expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (Trk B), while increasing glial fibrillary acidic protein expression and pro-BDNF, p75, NO, and iNOS levels. In Fat-1 mice, LPS-induced behavioral changes were attenuated, which were associated with decreased pro-inflammatory cytokines and reversed changes in p75, NO, iNOS, and BDNF. Gas chromatography assay confirmed increased n-3 PUFA levels and n-3/n-6 ratios in the brains of Fat-1 mice. In conclusion, endogenous n-3 PUFAs may improve LPS-induced depression-like behavior through balancing M1 and M2-phenotypes and normalizing BDNF function.

Authors+Show Affiliations

Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. guminqingwawa@163.com.Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. YUYULI2016@163.com.Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. THT19118@126.com.Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. zhangcai910206@163.com. Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. zhangcai910206@163.com.Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang 524023, China. lwd@gdlami.com. Guangdong Key laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring Institute, Guangzhou 510663, China. lwd@gdlami.com.Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. zhangyp2015@163.com. Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. zhangyp2015@163.com.Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. m13246531887@163.com.Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. yuntaozhao@163.com. Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. yuntaozhao@163.com.Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. cai.song@dal.ca. Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. cai.song@dal.ca. Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada. cai.song@dal.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30248907

Citation

Gu, Minqing, et al. "Endogenous Omega (n)-3 Fatty Acids in Fat-1 Mice Attenuated Depression-Like Behavior, Imbalance Between Microglial M1 and M2 Phenotypes, and Dysfunction of Neurotrophins Induced By Lipopolysaccharide Administration." Nutrients, vol. 10, no. 10, 2018.
Gu M, Li Y, Tang H, et al. Endogenous Omega (n)-3 Fatty Acids in Fat-1 Mice Attenuated Depression-Like Behavior, Imbalance between Microglial M1 and M2 Phenotypes, and Dysfunction of Neurotrophins Induced by Lipopolysaccharide Administration. Nutrients. 2018;10(10).
Gu, M., Li, Y., Tang, H., Zhang, C., Li, W., Zhang, Y., ... Song, C. (2018). Endogenous Omega (n)-3 Fatty Acids in Fat-1 Mice Attenuated Depression-Like Behavior, Imbalance between Microglial M1 and M2 Phenotypes, and Dysfunction of Neurotrophins Induced by Lipopolysaccharide Administration. Nutrients, 10(10), doi:10.3390/nu10101351.
Gu M, et al. Endogenous Omega (n)-3 Fatty Acids in Fat-1 Mice Attenuated Depression-Like Behavior, Imbalance Between Microglial M1 and M2 Phenotypes, and Dysfunction of Neurotrophins Induced By Lipopolysaccharide Administration. Nutrients. 2018 Sep 21;10(10) PubMed PMID: 30248907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous Omega (n)-3 Fatty Acids in Fat-1 Mice Attenuated Depression-Like Behavior, Imbalance between Microglial M1 and M2 Phenotypes, and Dysfunction of Neurotrophins Induced by Lipopolysaccharide Administration. AU - Gu,Minqing, AU - Li,Yuyu, AU - Tang,Haiting, AU - Zhang,Cai, AU - Li,Wende, AU - Zhang,Yongping, AU - Li,Yajuan, AU - Zhao,Yuntao, AU - Song,Cai, Y1 - 2018/09/21/ PY - 2018/08/08/received PY - 2018/08/27/revised PY - 2018/09/04/accepted PY - 2018/9/26/entrez PY - 2018/9/27/pubmed PY - 2018/12/18/medline KW - BDNF KW - Fat-1 transgenic mice KW - depression KW - microglial M1 and M2 phenotypes KW - n-3 fatty acids KW - neurotrophins JF - Nutrients JO - Nutrients VL - 10 IS - 10 N2 - n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve depression. However, PUFA purities, caloric content, and ratios in different diets may affect the results. By using Fat-1 mice which convert n-6 to n-3 PUFAs in the brain, this study further evaluated anti-depressant mechanisms of n-3 PUFAs in a lipopolysaccharide (LPS)-induced model. Adult male Fat-1 and wild-type (WT) mice were fed soybean oil diet for 8 weeks. Depression-like behaviors were measured 24 h after saline or LPS central administration. In WT littermates, LPS reduced sucrose intake, but increased immobility in forced-swimming and tail suspension tests. Microglial M1 phenotype CD11b expression and concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-17 were elevated, while M2 phenotype-related IL-4, IL-10, and transforming growth factor (TGF)-β1 were decreased. LPS also reduced the expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (Trk B), while increasing glial fibrillary acidic protein expression and pro-BDNF, p75, NO, and iNOS levels. In Fat-1 mice, LPS-induced behavioral changes were attenuated, which were associated with decreased pro-inflammatory cytokines and reversed changes in p75, NO, iNOS, and BDNF. Gas chromatography assay confirmed increased n-3 PUFA levels and n-3/n-6 ratios in the brains of Fat-1 mice. In conclusion, endogenous n-3 PUFAs may improve LPS-induced depression-like behavior through balancing M1 and M2-phenotypes and normalizing BDNF function. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/30248907/Endogenous_Omega__n__3_Fatty_Acids_in_Fat_1_Mice_Attenuated_Depression_Like_Behavior_Imbalance_between_Microglial_M1_and_M2_Phenotypes_and_Dysfunction_of_Neurotrophins_Induced_by_Lipopolysaccharide_Administration_ L2 - http://www.mdpi.com/resolver?pii=nu10101351 DB - PRIME DP - Unbound Medicine ER -