Duloxetine ameliorates lipopolysaccharide-induced microglial activation by suppressing iNOS expression in BV-2 microglial cells

• Published in: Psychopharmacology 2022-10, Vol.239 (10), p.3133-3143
• Main Authors: Nakatani, Yoshihiko, Yaguchi, Manami, Ogino, Kazuki, Noguchi, Risako, Yamamoto, Naoki, Amano, Taku
• Format: Article
• Language: English
• Subjects: AKT protein; Biomedical and Life Sciences; Biomedicine; Drug therapy; Duloxetine; Health aspects; Inflammation; Lipopolysaccharides; Major depressive disorder; Microglial cells; Neurosciences; Nitric-oxide synthase; Norepinephrine; Original Investigation; Oxidoreductases; Pharmacology/Toxicology; Phosphorylation; Physiological aspects; Protein expression; Proteins; Psychiatry; Serotonin uptake inhibitors; Synaptic cleft
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-022-06194-6

Rationale It is known that both selective serotonin and serotonin noradrenaline reuptake inhibitors (SSRI, SNRI) are first-line drugs for the treatment of major depressive disorder. It has also been considered that both SSRI and SNRI can improve the symptoms of major depressive disorder by increasing the concentration of monoamine in the synaptic cleft based on the monoamine hypothesis. However, accumulating evidence has indicated that inflammation in the brain may be a key factor in the pathophysiological mechanisms that underlie the development of major depressive disorder. Objectives It has been advocated that microglial cells may regulate the inflammatory response under pathological conditions such as major depressive disorder. In this study, we focused on whether duloxetine can ameliorate the inflammatory response induced by lipopolysaccharide (LPS) in BV-2 microglial cells. Results Our results indicated that duloxetine significantly decreased the NO production induced by LPS. The increase in the protein expression level of iNOS induced by LPS was significantly decreased by treatment with duloxetine. Moreover, the increases in the protein expression levels of phosphorylated-IκBα, phosphorylated-Akt and Akt induced by LPS were also significantly decreased. Unexpectedly, the protein expression levels of other pro-inflammatory factors such as COX-2 and the phosphorylation ratios for various molecules including IκBα and Akt were not changed by treatment with duloxetine. Conclusions These findings suggest that duloxetine may have an anti-inflammatory effect, which could contribute to its therapeutic effectiveness for major depressive disorder.