Knockout of vitronectin increased EAE lesion pathology without affecting demyelination and motor deficits
Abstract
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system affecting more women than men that lacks both effective chronic-phase disease treatment and a final cure. Rodent experimental autoimmune encephalomyelitis (EAE) mimics MS pathology through T-cell infiltration, inflammation, and motor deficits measured by clinical sign scores. Vitronectin (VTN) has been shown to leak and accumulate in EAE lesions, activating microglia and astrocytes. Here, we investigated whether knockout of VTN affected EAE progression and lesion pathology. EAE was induced in both female and male VTN+/+ and VTN-/- mice using MOG35-55. Clinical scores were measured daily with peak scores found between days 15- 20 in both sexes, consistent with previous work in C57BL/6 mice. Scores reached a steady state, i.e., chronic disease phase, after 21-23 days. Clinical signs were reduced in female mice only in both acute and chronic disease phases with an overall reduction in peak score. At 35 days, demyelination measured by eriochrome cyanine R (EC) staining was reduced in VTN-/- female mice, but not in males. Astrocyte activation measured by GFAP was also decreased in VTN-/- females only, but microglia activation and leukocyte infiltration measured by CD68 and CD45, respectively, were unaffected in both sexes. Cuprizone-mediated demyelination (CPZ) is a toxin-induced MS model to study demyelination and remyelination that is not significantly attributed to the peripheral immune system. To test the effect of VTN on the CPZ model, we administered 0.2% cuprizone in powdered chow to female VTN+/+ and VTN-/- mice for 12 weeks. VTN-/- motor deficits and demyelination shown through EC staining were comparable to sham controls, while VTN+/+ mice showed significant demyelination in the corpus callosum and reduced motor function. Together, these data suggest that VTN is detrimental in EAE models, increasing clinical signs and demyelination through astrocyte activation.
Start Time
15-4-2026 9:00 AM
End Time
15-4-2026 12:00 PM
Room Number
Culp Ballroom 316
Poster Number
14
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Science, Technology, and Engineering
Student Type
Graduate and Professional Degree Students, Residents, Fellows
Faculty Mentor
Cuihong Jia
Knockout of vitronectin increased EAE lesion pathology without affecting demyelination and motor deficits
Culp Ballroom 316
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system affecting more women than men that lacks both effective chronic-phase disease treatment and a final cure. Rodent experimental autoimmune encephalomyelitis (EAE) mimics MS pathology through T-cell infiltration, inflammation, and motor deficits measured by clinical sign scores. Vitronectin (VTN) has been shown to leak and accumulate in EAE lesions, activating microglia and astrocytes. Here, we investigated whether knockout of VTN affected EAE progression and lesion pathology. EAE was induced in both female and male VTN+/+ and VTN-/- mice using MOG35-55. Clinical scores were measured daily with peak scores found between days 15- 20 in both sexes, consistent with previous work in C57BL/6 mice. Scores reached a steady state, i.e., chronic disease phase, after 21-23 days. Clinical signs were reduced in female mice only in both acute and chronic disease phases with an overall reduction in peak score. At 35 days, demyelination measured by eriochrome cyanine R (EC) staining was reduced in VTN-/- female mice, but not in males. Astrocyte activation measured by GFAP was also decreased in VTN-/- females only, but microglia activation and leukocyte infiltration measured by CD68 and CD45, respectively, were unaffected in both sexes. Cuprizone-mediated demyelination (CPZ) is a toxin-induced MS model to study demyelination and remyelination that is not significantly attributed to the peripheral immune system. To test the effect of VTN on the CPZ model, we administered 0.2% cuprizone in powdered chow to female VTN+/+ and VTN-/- mice for 12 weeks. VTN-/- motor deficits and demyelination shown through EC staining were comparable to sham controls, while VTN+/+ mice showed significant demyelination in the corpus callosum and reduced motor function. Together, these data suggest that VTN is detrimental in EAE models, increasing clinical signs and demyelination through astrocyte activation.
