Electroacupuncture Relieves LPS-Induced Depression-Like Behaviour in Rats Through IDO-Mediated Tryptophan-Degrading Pathway

Abstract

Background

Neuroinflammation is an important pathological mechanism of depression that leads to an increase in indoleamine-2,3-dioxygenase (IDO) activity and NMDAR activation. This study aimed to observe the effects of electroacupuncture on depression-like behaviour in lipopolysaccharide (LPS)-treated rats and the underlying mechanism.

Methods

Wistar rats were intraperitoneally administered LPS (0.5 mg/kg) for 7 consecutive days to establish a depression model. Electroacupuncture treatment was administered 1 hour after daily LPS injection. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to evaluate the depressive-like behaviours. IL-1β, IL-6, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA); Trp, 5-hydroxytryptamine (5-HT), kynurenine (Kyn) and quinolinic acid (Quin) were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry; and N-methyl-D-aspartate receptor (NMDAR) protein and mRNA were assessed by Western blot and real-time qPCR.

Results

The results showed that electroacupuncture treatment successfully corrected LPS-induced depressive-like behaviour, reduced the inflammatory factor (IL-1β, IL-6 and TNF-α) levels in the blood and hippocampus, prevented IDO over-activation and recovered NR2B expression after challenge by LPS.

Conclusion

Electroacupuncture treatment provided protection against LPS-induced depressive-like behaviour, and the associated mechanisms may be related to inhibiting the inflammatory response, regulating the IDO-mediated tryptophan-degrading pathway, and inhibiting NR2B activation.

Keywords:

• depression
• electroacupuncture
• LPS
• IDO

Acknowledgments

This research was funded by grants from the Science and Technology Commission of Shanghai Municipality, china (Grant No. 18401970600) and Shanghai Municipal Health and Family Planning Commission (Grant No. ZY(2018-2020)-CCCX-1005).

Abbreviations

IDO, indoleamine 2,3-dioxygenase; 5-HT, 5-hydroxytryptamine; UHPLC-MS/MS, Ultra-high-performance liquid chromatography-tandem mass spectrometry; FST, forced swimming test; OFT, open field test; SPT, sucrose preference test; Trp, tryptophan; LPS, lipopolysaccharide; Kyn, kynurenine; Quin, quinolinic acid.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.