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Inflammopharmacology. 2019 Nov 30. doi: 10.1007/s10787-019-00668-4. [Epub ahead of print]

Analysis of brain metabolites by gas chromatography-mass spectrometry reveals the risk-benefit concerns of prednisone in MRL/lpr lupus mice.

Author information

1
Institute of TCM Clinical Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
2
The Second Affiliated Hospital of Zhejiang, Chinese Medical University, Hangzhou, 310005, Zhejiang, China.
3
Epilepsy Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
4
Institute of TCM Clinical Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China. wengcp@163.com.
5
Institute of TCM Clinical Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China. xuzhenghao@zcmu.edu.cn.

Abstract

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.

KEYWORDS:

Brain; Gas chromatography-mass spectrometry; Glucocorticoids; Lupus; Metabolomics

PMID:
31786803
DOI:
10.1007/s10787-019-00668-4

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