Abstract
Neuroinflammation contributes to the pathogenesis of depression. Inulin-type oligosaccharides of Morinda officinalis (IOMO) exert antidepressant-like effects in rodents and patients with depression, while the underlying mechanisms remain unclear. This study used chronic restraint stress (CRS) and lipopolysaccharide (LPS) to induce depression-like behaviors in mice. Western blotting and ELISA analysis were used to investigate the effects of IOMO on inflammatory cytokine levels. Immunofluorescence analysis was used to investigate the effects of IOMO on hippocampal NLRP3 inflammasome and microglial cells. The results suggested that 6 weeks of CRS induced significant depression-like behaviors based on the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST), which were accompanied by increases in the expression of IL-6 and the activation of hippocampal microglial cells. Chronic treatment with IOMO (25 mg/kg, i.g.) for 28 days significantly reversed these depression-like behaviors and inhibited the activation of microglial cells. Furthermore, LPS (0.5 mg/kg, i.p.) also significantly induced depression-like behaviors in the TST, FST, and novelty-suppressed feeding test (NSFT), as well as increased the expression of IL-1β and caspase-1, and activated the microglial cells and the NLRP3 inflammasome in the hippocampus. Treatment with IOMO for 9 days significantly reversed these depression-like behaviors and normalized the LPS-induced activation of the microglial cells and NLRP3 inflammasome. Taken together, these results suggested that IOMO exerted antidepressant-like effects via hippocampal microglial NLRP3 inflammasome mediation followed by caspase-1 inhibition and the production of IL-1β. These findings provide a basis for developing new antidepressants targeting the microglial NLRP3 inflammasome.
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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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This work was supported by STI2030-Major Projects (No. 2021ZD0200900) and the National Natural Science Foundation of China (No. 81773708).
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Zhao-Kai Lai and Yong-Yu Yin performed the research design, behavioral tests, immunofluorescence, ELISA, western blotting experiments, data analysis, and wrote the manuscript. Jiao-Zhao Yan contributed to the behavioral tests and immunofluorescence experiments. Qian-Qian Wei helped with the behavioral tests and writing the manuscript. Bin Wang helped with the immunofluorescence experiments. Yun-Feng Li, Li-Ming Zhang, and Yu-Lu Wang contributed to the research design and revised the manuscript. All authors approved the final manuscript.
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Lai, ZK., Yin, YY., Yan, JZ. et al. Inulin-type oligosaccharides of Morinda officinalis exerted antidepressant effects by reducing hippocampal inflammation. Metab Brain Dis 38, 2065–2075 (2023). https://doi.org/10.1007/s11011-023-01223-5
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DOI: https://doi.org/10.1007/s11011-023-01223-5