Endogenic 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

Prof. Cai Song  cai.song@dal.ca

 

Background

Omega (n)-3 polyunsaturated Omega (n)-3 fatty acids (PUFAs) may treat depression through anti-inflammation and benefiting neurotrophin function. However, these results were from oral administration to human or rodent models. The purities, calories and different PUFA ratios in the n-3 PUFA diets were various. Moreover, n-3 PUFA metabolism and interaction with other food components in the digestive system are unknown. By using fat-1 mice which can convert n-6 to n-3 PUFAs in the brain, the present study was to evaluate anti-depression, anti-inflammatory and neuroprotective mechanism in a lipopolysaccharide (LPS)-induced model of depression.

 

Methods

Adult male fat-1 mice and their wild type (WT) littermates were fed soybean oil diet. Depression- and anxiety-like behaviors were measured 24 h after intracerebroventricular infusion of saline or LPS.  Brain PUFA profile was assayed by GC, microglia phone types and related markers, as well as the expression neurotrophic factors were measured by ELISA, qPCR and western blot respectively in the hippocampus. 

 

Results

In WT littermates, LPS down-regulated sucrose preference, while increased immobility times in the forced-swimming test. The expression of microglial M1 phenotype CD11b and pro-inflammation IL-1β, TNF-α, IL-17 were up-regulated, but M2 phenotype Arg-1 and TGF-β1 were down regulated. LPS also reduced the expression of BDNF and TrkB, but increased proBDNF, p75, NO and iNOS. In fat-1 mice, these depression-like behaviors were attenuated, the imbalance between in M1 and M2 phenotypes were restored and BDNF and receptor functions returned to normal in fat-1 mice. These changes are associated with increased EPA, DHA , n-3 PUFAs and n-3 FAs/ n-6 FAs ratios. 

 

Conclusion

Endogenic n-3 PUFAs in fat-1 mice improve LPS-induced inflammatory changes, alleviate depression-like behavior through restoring imbalance between M1 and M2, pro- and anti-inflammatory and mature and pro-BNDF and their receptors.