PMID- 30248907 OWN - NLM STAT- MEDLINE DCOM- 20181217 LR - 20181217 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 10 IP - 10 DP - 2018 Sep 21 TI - 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. LID - 10.3390/nu10101351 [doi] LID - 1351 AB - 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)-1beta, tumor necrosis factor (TNF)-alpha, and IL-17 were elevated, while M2 phenotype-related IL-4, IL-10, and transforming growth factor (TGF)-beta1 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. FAU - Gu, Minqing AU - Gu M AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. guminqingwawa@163.com. FAU - Li, Yuyu AU - Li Y AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. YUYULI2016@163.com. FAU - Tang, Haiting AU - Tang H AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. THT19118@126.com. FAU - Zhang, Cai AU - Zhang C AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. zhangcai910206@163.com. AD - Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. zhangcai910206@163.com. FAU - Li, Wende AU - Li W AD - Guangdong Key Laboratory for Research and Development of Natural Drug, Guangdong Medical College, Zhanjiang 524023, China. lwd@gdlami.com. AD - Guangdong Key laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring Institute, Guangzhou 510663, China. lwd@gdlami.com. FAU - Zhang, Yongping AU - Zhang Y AUID- ORCID: 0000-0002-8667-860X AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. zhangyp2015@163.com. AD - Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. zhangyp2015@163.com. FAU - Li, Yajuan AU - Li Y AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. m13246531887@163.com. FAU - Zhao, Yuntao AU - Zhao Y AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. yuntaozhao@163.com. AD - Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. yuntaozhao@163.com. FAU - Song, Cai AU - Song C AD - Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China. cai.song@dal.ca. AD - Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China. cai.song@dal.ca. AD - Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada. cai.song@dal.ca. LA - eng GR - 81471223/National Natural Science Foundation of China/ GR - 2016B020235001 and 2016A020215153/Guangdong Science and Technology Department/ GR - KY20170210/Shenzhen Dapeng District industrial development special funds for science and technology support project/ PT - Journal Article DEP - 20180921 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (CD11b Antigen) RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Cytokines) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fatty Acids, Omega-6) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (Nerve Growth Factors) RN - 0 (fat-1 protein, C elegans) RN - EC 1.14.19.- (Fatty Acid Desaturases) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Animals MH - Behavior, Animal/drug effects/physiology MH - Brain/drug effects/*metabolism MH - Brain-Derived Neurotrophic Factor/*metabolism MH - *CD11b Antigen MH - Caenorhabditis elegans Proteins/genetics/metabolism MH - Cytokines/metabolism MH - Depression/etiology/*metabolism MH - Depressive Disorder/metabolism MH - Diet MH - Fatty Acid Desaturases/genetics/metabolism MH - Fatty Acids, Omega-3/*metabolism/pharmacology MH - Fatty Acids, Omega-6/metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Hindlimb Suspension MH - Inflammation/chemically induced/complications/*metabolism MH - Lipopolysaccharides MH - Membrane Glycoproteins/metabolism MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Microglia/drug effects/*metabolism MH - Nerve Growth Factors/metabolism MH - Phenotype MH - Protein-Tyrosine Kinases/metabolism MH - Swimming PMC - PMC6213921 OTO - NOTNLM OT - BDNF OT - Fat-1 transgenic mice OT - depression OT - microglial M1 and M2 phenotypes OT - n-3 fatty acids OT - neurotrophins COIS- The authors declare that they have no conflicts of interest. EDAT- 2018/09/27 06:00 MHDA- 2018/12/18 06:00 PMCR- 2018/10/01 CRDT- 2018/09/26 06:00 PHST- 2018/08/08 00:00 [received] PHST- 2018/08/27 00:00 [revised] PHST- 2018/09/04 00:00 [accepted] PHST- 2018/09/26 06:00 [entrez] PHST- 2018/09/27 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] PHST- 2018/10/01 00:00 [pmc-release] AID - nu10101351 [pii] AID - nutrients-10-01351 [pii] AID - 10.3390/nu10101351 [doi] PST - epublish SO - Nutrients. 2018 Sep 21;10(10):1351. doi: 10.3390/nu10101351.