Objective

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common cause of disability in systemic lupus erythematosus (SLE). This study aims to investigate the metabolic changes in the hypothalamus and frontal cortex in lupus-prone MRL/lpr mice.

Methods

Metabolic changes were analyzed using gas chromatography-mass spectrometry (GC–MS).

Results

According to the principal component analysis (PCA), the metabolic profiles were different between the frontal cortex and hypothalamus, but they were comparable between MRL/lpr and MRL/MpJ mice (16 weeks of age). By OPLS-DA, eight cortical and six hypothalamic differential metabolites were identified in MRL/lpr as compared to MRL/MpJ mice. Among these differential metabolites, we found a decrease of N-acetyl-l-aspartate (NAA, a potential marker of neuronal integrity), an increase of pyruvate and a decrease of glutamate in the frontal cortex but not in the hypothalamus. Prednisone treatment (3 mg/kg from 8 weeks of age) relieved the decrease of NAA but further increased the accumulation of pyruvate in the frontal cortex, additionally affected eight enriched pathways in the hypothalamus, and led to significant imbalances between the excitation and inhibition in both the frontal cortex and hypothalamus.

Conclusion

These results suggest that the frontal cortex may be more preferentially affected than the hypothalamus in SLE. Prednisone disrupted rather than relieved metabolic abnormalities in the brain, especially in the hypothalamus, indicating that the risk–benefit balance of prednisone for SLE or NPSLE remains to be further evaluated.

中文翻译：

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通过气相色谱-质谱法对脑代谢产物的分析揭示了泼尼松在MRL / lpr狼疮小鼠中的风险-收益问题。

目的

神经精神性系统性红斑狼疮（NPSLE）是系统性红斑狼疮（SLE）致残的常见原因。这项研究旨在调查易患狼疮的MRL / lpr小鼠下丘脑和额叶皮层的代谢变化。

方法

使用气相色谱-质谱（GC-MS）分析了代谢变化。

结果

根据主成分分析（PCA），额叶皮层和下丘脑之间的代谢谱不同，但MRL / lpr和MRL / MpJ小鼠（16周龄）的代谢谱具有可比性。通过OPLS-DA，与MRL / MpJ小鼠相比，在MRL / lpr中鉴定出8种皮质和6种下丘脑差异代谢产物。在这些差异代谢物中，我们发现N-乙酰基-l含量降低-天冬氨酸（NAA，神经元完整性的潜在标志物），额叶皮质中丙酮酸的增加和谷氨酸的减少，但在下丘脑中没有。泼尼松治疗（从8周龄开始为3 mg / kg）减轻了NAA的降低，但进一步增加了额叶皮质中丙酮酸的积累，还影响了下丘脑的8个富集途径，并导致兴奋和抑制之间的显着失衡。额叶皮层和下丘脑。

结论

这些结果表明，与SLE下丘脑相比，额叶皮层可能受到更优先的影响。泼尼松破坏而不是缓解了大脑，尤其是下丘脑的代谢异常，这表明泼尼松对SLE或NPSLE的风险-获益平衡尚待进一步评估。