Mild Disease Course of Experimental Autoimmune Encephalomyelitis without Pertussis Toxin: Brain Transcriptome Analysis Reveals Similar Signaling to Active Lesions in Multiple Sclerosis
ORCID
Kaplan: https://orcid.org/0000-0002-1992-4145
MSU Affiliation
College of Veterinary Medicine; Department of Comparative Biomedical Sciences; Center for Environmental Health Sciences
Creation Date
2026-03-30
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a powerful model to study multiple sclerosis (MS). One of the approaches for EAE is to actively immunize with myelin-derived peptides with immune adjuvants. One of the commonly used immune adjuvants is pertussis toxin (PTx), without which EAE disease is mild with relatively longer onset. However, pertussis toxin can also inhibit G protein-coupled receptor (GPCR) signaling so it can confound investigations into the role of GPCRs in EAE or therapies designed to target GPCRs. Since EAE via active immunization without PTx results in a relatively mild disease state, we wanted to confirm that appropriate signaling molecules for the disease were being induced in one target tissue (i.e., brain). RNA-Seq analysis of whole brain tissue demonstrated that the MS signaling pathway was strongly activated in symptomatic mice. In addition, there was activation of Th1 (IFN signaling), Th2 (IL-4 signaling), and Th17 (IL-17 signaling). In comparing canonical pathways from our mouse mild EAE brains with a human MS atlas, EAE shared the most pathways with active and inactive lesions. An advantage of this approach is that disease induction is slower to develop and results in modest clinical signs, which likely more closely mimic human disease onset.
Publication Date
5-30-2024
Publication Title
Biomedicines
Publisher
MDPI
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Frodella, C. M., Pruett, S. B., & Kaplan, B. L. F. (2024). Mild Disease Course of Experimental Autoimmune Encephalomyelitis without Pertussis Toxin: Brain Transcriptome Analysis Reveals Similar Signaling to Active Lesions in Multiple Sclerosis. Biomedicines, 12(6), 1215. https://doi.org/10.3390/biomedicines12061215
