Abstract
Objective
To investigate whether glucocorticoids, the hallmark medication for systemic lupus erythematosus (SLE), could prevent the development of neuropsychiatric SLE (NPSLE).
Methods
The protective effects of prednisone on NPSLE were tested using the open field, object recognition/placement, forced swim, tail suspension, and sucrose preference tests in MRL/lpr mice. Auto-antibody titres and the weight of lymph nodes were also measured.
Results
MRL/lpr mice exhibited mild depression at the age of 8 weeks before progressing with spatial cognitive impairment and severe depression-like behaviour at the age of 16 weeks. Treating MRL/lpr mice with prednisone (5 mg/kg) from the age of 8 weeks decreased anti-cardiolipin and anti-N-methyl-d-aspartate (NMDA) receptor antibody titres in the brain, reduced the weight of lymph nodes, and prolonged the floating latency in the forced swim test. However, prednisone (3 or 5 mg/kg) had no preventive effect on the development of spatial cognitive impairment and other depression-like behaviours in MRL/lpr mice. The dose of prednisone had a positive correlation with the floating latency in the forced swim test, while it offered no effects on all other behavioural tests.
Conclusion
Our results provide evidence that early treatment with prednisone had a limited effect on the development of neuropsychiatric symptoms in MRL/lpr mice. Further work is needed in other models beyond NPSLE in MRL/lpr mice before any definitive conclusions are made on the efficacy of prednisone in human NPSLE.
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Abbreviations
- ACA:
-
Anti-cardiolipin antibody
- ANOVA:
-
One-way analysis of variance
- Anti-NMDAR:
-
Anti-N-methyl-d-aspartate receptor
- ELISA:
-
Enzyme-linked immunosorbent assays
- EULAR:
-
European league against rheumatism
- i.g.:
-
Intragastrically
- LPR-8w:
-
8-Week-old MRL/lpr mice
- NPSLE:
-
Neuropsychiatric systemic lupus erythematosus
- NMDAR:
-
N-Methyl-D-aspartate receptor
- PRE:
-
Prednisone
- PRE-3 mg:
-
Prednisone at 3 mg/kg
- PRE-5 mg:
-
Prednisone at 5 mg/kg
- SLE:
-
Systemic lupus erythematosus
- WT:
-
Wild type
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Acknowledgements
This work was funded by the Zhejiang TCM Science and Technology Plan (2018ZZ007), the National Natural Science Foundation of China (81673623), and partly the Foundation of the Zhejiang Chinese Medical University (ZYX2018002 and 2018ZG24). The authors thank the members of the Laboratory Animal Research Centre of Zhejiang Chinese Medical University for their excellent technical support. The authors also thank Dr. John Hugh Snyder and Dr. Anthony J. Filiano for editing our manuscript. Z. X. also would like to thank all members of Filiano Lab, Kurtzberg Lab and Marcus Centre for Cellular Cures (MC3) at Duke University.
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Lu, F., Lu, H., Xie, M. et al. Limited preventive effect of prednisone on neuropsychiatric symptoms in murine systemic lupus erythematosus. Inflammopharmacol 27, 511–520 (2019). https://doi.org/10.1007/s10787-019-00587-4
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DOI: https://doi.org/10.1007/s10787-019-00587-4