Abstract
Multiple sclerosis (MS) is characterized by neuroinflammation and neurodegeneration, whose precise processes are not fully understood. Diacylglycerol kinase (DGK) isozymes of α, β, γ and ζ expressed abundantly in the brain and/or the immune system, may be regulatory targets for MS. In this study, we analyzed the four DGK isozymes along the induction, peak and recovery phases in an experimental autoimmune encephalomyelitis (EAE) rat model of MS. The expression of these DGK isozymes and the diacylglycerol (DAG) pathway in the EAE rat brainstems were analyzed by qRT-PCR, immunohistochemistry, immunofluorescence double staining, western blotting and ELISA. Our results showed that the mRNA content of the four DGK isozymes decreased significantly, and their immunoreactivity in myelin sheathes (DGKα, β) and neurons (DGKγ, ζ) became weaker at the beginning of the induction phase. With the progressive increase in clinical signs, DGKα, DGKγ and DGKζ mRNA increased and DGKβ mRNA decreased, and microglia were involved in the formation of perivascular cuffing. In the peak phase, both DGKα and DGKζ were expressed in neurons and inflammatory cells, and DGKζ was also positive in microglia. During the recovery phase, the mRNA content and immunoreactivity of these DGK isozymes generally reached normal levels. Moreover, our results revealed that changes in DAG accumulation and PKCδ phosphorylation were almost the same as those of DGKα and DGKζ mRNA. In summary, the four DGK isozymes are involved in the EAE process. The predominant and broad presence of DGKα and DGKζ suggests that they may regulate the pathological process by attenuating DAG/PKCδ pathway signaling during EAE evolution.
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This study was supported by the National Natural Science Foundation of China (81371254), Natural Science Foundation of Shanxi Province (2008011079-2), and the Science and Technology Innovation Foundation of Shanxi Medical University (01200719).
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This study was supported by the National Natural Science Foundation of China (81371254), Natural Science Foundation of Shanxi Province (2008011079-2), Science and Technology Innovation Foundation of Shanxi Medical University (01200719).
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Conceptualization: YZ, HC and JM. Methodology and analysis: HC, YH, YW, JM, XC and JX. The first draft of the manuscript was written by HC, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Cui, H., Huang, Y., Wu, Y. et al. The expression of diacylglycerol kinase isoforms α and ζ correlates with the progression of experimental autoimmune encephalomyelitis in rats. Histochem Cell Biol 156, 437–448 (2021). https://doi.org/10.1007/s00418-021-02011-x
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DOI: https://doi.org/10.1007/s00418-021-02011-x