Deletion of beta-2-microglobulin ameliorates spinal cord lesion load and promotes recovery of brainstem NAA levels in a murine model of multiple sclerosis

Aleksandar Denic, Istvan Pirko, Bharath Wootla, Allan Bieber, Slobodan I Macura, Moses Rodriguez

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We used genetic deletion of β2-microglobulin to study the influence of CD8+ T cells on spinal cord demyelination, remyelination, axonal loss and brainstem N-acetyl aspartate levels during the acute and chronic phases of Theiler's murine encephalomyelitis virus (TMEV) infection. We used β2m-/- and β2m+/+ B10.Q mice (of H-2q background) normally susceptible to TMEV-induced demyelination. Over the disease course, β2m+/+ mice had increasing levels of demyelination and minimal late-onset remyelination. In contrast, β2m -/- mice had steady levels of demyelination from 45-390 dpi and remyelination was extensive and more complete. Early in the disease, brainstem NAA levels drop in both strains, but accordingly with remyelination and axonal preservation, NAA recover in β2m-/- mice despite equivalent brainstem pathology. At 270 dpi, β2m+/+ mice had significantly fewer spinal cord axons than β2m-/- mice (up to 28% less). In addition, β2m+/+ mice lost axons of all calibers, whereas β2m-/- mice had a modest loss of only medium- and large-caliber axons. This study further supports the hypothesis that CD8+ T cells are involved in demyelination, and axonal loss following Theiler's virus-induced demyelination.

Original languageEnglish (US)
Pages (from-to)698-708
Number of pages11
JournalBrain Pathology
Volume22
Issue number5
DOIs
StatePublished - Sep 2012

Fingerprint

beta 2-Microglobulin
Brain Stem
Multiple Sclerosis
Spinal Cord
Demyelinating Diseases
Theilovirus
Axons
T-Lymphocytes
Virus Diseases
Pathology

Keywords

  • axonal loss
  • beta-2-microglobulin
  • demyelination
  • N-acetyl aspartate (NAA)
  • Theiler's murine encephalomyelitis virus (TMEV)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Deletion of beta-2-microglobulin ameliorates spinal cord lesion load and promotes recovery of brainstem NAA levels in a murine model of multiple sclerosis. / Denic, Aleksandar; Pirko, Istvan; Wootla, Bharath; Bieber, Allan; Macura, Slobodan I; Rodriguez, Moses.

In: Brain Pathology, Vol. 22, No. 5, 09.2012, p. 698-708.

Research output: Contribution to journalArticle

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