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
Open accessAbstract
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.
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Preclinical studies in rodents show that IL-17A administration induces depressive-like behaviors and stress exposure elevates IL-17A levels.
“Preclinical studies in rodents corroborate these findings, showing that IL-17A administration induces depressive-like behaviors [48] and stress exposure elevates IL-17A levels [66,67,68,69].”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [67]
Results §3.3 reports elevated hippocampal IL-17 in mice after LPS injection, alongside the depression-like behaviors described in the Discussion. It does not show that stress exposure elevates IL-17A: the Discussion’s example of a stress-related cytokine increase concerns IL-13 after acute foot shock. The paper also does not report administering IL-17A to induce depressive-like behavior. (LLM, conf=0.78)
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- Authors
- Gu, M., Li, Y., Tang, H., Zhang, C., Li, W., Zhang, Y., Li, Y., Zhao, Y., & Song, C.
- Affiliations
- Guangdong Ocean University (CN)
- Guangdong Medical College (CN)
- Research Institute for Marine Drug and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
- Dalhousie University (CA)
- Corresponding author
- Song, Cai
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2018-09-21
- Volume
- 10
- Issue
- 10
- Pages
- 1351
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC6213921
- OpenAlex
- W2890491720
- Cited by
- 73
- References
- 59
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 5 · 2023: 16 · 2022: 12 · 2021: 9 · 2020: 12 · 2019: 4
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81471223)
- Guangdong Science and Technology Department (2016B020235001 and 2016A020215153)
- Shenzhen Dapeng District industrial development special funds for science and technology support project (KY20170210)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- omega-3 fatty acids, fat-1 mice, depression-like behavior, lipopolysaccharide, neuroinflammation, brain-derived neurotrophic factor, proBDNF, p75 neurotrophin receptor, nitric oxide, inducible nitric oxide synthase, n-6/n-3 ratio, anti-inflammatory cytokines, neuroprotection
- MeSH terms
- Animals, Behavior, Animal, Brain, Depression, Depressive Disorder, Diet, Glial Fibrillary Acidic Protein, Inflammation, Lipopolysaccharides, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, Nerve Growth Factors, Phenotype, Protein-Tyrosine Kinases, Swimming, Fatty Acids, Omega-3, Cytokines, Microglia, Brain-Derived Neurotrophic Factor, Hindlimb Suspension, Receptor, trkB, Caenorhabditis elegans Proteins, CD11b Antigen, Fatty Acids, Omega-6, Fatty Acid Desaturases
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