Journal article
Tumor necrosis factor receptor 2 activation elicits sex-specific effects on cortical myelin proteins and functional recovery in a model of multiple sclerosis
Brain research bulletin, v 207, p110885
Feb 2024
PMID: 38246200
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Multiple sclerosis (MS), a demyelinating autoimmune disease of the central nervous system (CNS), predominately affects females compared to males. Tumor necrosis factor (TNF), a pro-inflammatory cytokine, signaling through TNF receptor 1 contributes to inflammatory disease pathogenesis. In contrast, TNF receptor 2 signaling is neuroprotective. Current anti-TNF MS therapies are shown to be detrimental to patients due to pleiotropic effects on both pro- and anti-inflammatory functions. Using a non-pertussis toxin (nPTX) experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice, we systemically administered a TNFR2 agonist (p53-sc-mTNF
) to investigate behavioral and pathophysiological changes in both female and male mice. Our data shows that TNFR2 activation alleviates motor and sensory symptoms in females. However, in males, the agonist only alleviates sensory symptoms and not motor. nPTX EAE induction in TNFR2 global knockout mice caused exacerbated motor symptoms in females along with an earlier day of onset, but not in males. Our data demonstrates that TNFR2 agonist efficacy is sex-specific for alleviation of motor symptoms, however, it effectively reduces mechanical hypersensitivity in both females and males. Altogether, these data support the therapeutic promise TNFR2 agonism holds as an MS therapeutic and, more broadly, to treat central neuropathic pain.
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Details
- Title
- Tumor necrosis factor receptor 2 activation elicits sex-specific effects on cortical myelin proteins and functional recovery in a model of multiple sclerosis
- Creators
- Kayla L Nguyen - George Washington UniversityIshaan J Bhatt - Drexel UniversityShruti Gupta - Department of Biology, Drexel University, Philadelphia, PA 19104, United States of AmericaNazaf Showkat - Drexel UniversityKathryn A Swanson - Drexel UniversityRoman Fischer - University of StuttgartRoland E Kontermann - University of StuttgartKlaus Pfizenmaier - University of StuttgartValerie Bracchi-Ricard - Drexel UniversityJohn R Bethea - George Washington University
- Publication Details
- Brain research bulletin, v 207, p110885
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Neurobiology and Anatomy; College of Arts and Sciences
- Web of Science ID
- WOS:001171362700001
- Scopus ID
- 2-s2.0-85183023007
- Other Identifier
- 991021822959704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences