Figure 2.

Potential Mechanisms Associated with n-3 PUFAs Antidepressant Effects via the Improvement of BBB Integrity. n-3 PUFAs can decrease the expression of MMP9 via mechanisms including direct inhibition of NF-κβ and AP-1, resulting in reduced transcription of MMP9 gene. Further, n-3 PUFAs indirectly decrease MMP9 transcription by reducing the levels of NF-κβ, IL-1β, and IL-6, which stimulate MMP9 synthesis. Collectively, this reduces the extracellular levels of MMP9 thus limiting its proteolytic effects on the BBB and ultimately depression. AP-1, Activator protein 1; BBB, Blood-brain barrier; FFAR4, Free fatty acid receptor 4; IL, Interleukin; MMP9, Matrix metalloproteinase 9; n-3 PUFAs, Omega-3 polyunsaturated fatty acids; NF-κβ, Nuclear factor kappa beta; NLRP3, Nucleotide-binding oligomerization domain-like receptor protein 3; TIMP-1, Tissue inhibitors of metalloproteinase-1; TNF, Tumor necrosis factor.