TY - JOUR
T1 - Deletion of beta-2-microglobulin ameliorates spinal cord lesion load and promotes recovery of brainstem NAA levels in a murine model of multiple sclerosis
AU - Denic, Aleksandar
AU - Pirko, Istvan
AU - Wootla, Bharath
AU - Bieber, Allan
AU - MacUra, Slobodan
AU - Rodriguez, Moses
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - N-acetyl aspartate (NAA)
KW - Theiler's murine encephalomyelitis virus (TMEV)
KW - axonal loss
KW - beta-2-microglobulin
KW - demyelination
UR - http://www.scopus.com/inward/record.url?scp=84865451385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865451385&partnerID=8YFLogxK
U2 - 10.1111/j.1750-3639.2012.00576.x
DO - 10.1111/j.1750-3639.2012.00576.x
M3 - Article
C2 - 22335434
AN - SCOPUS:84865451385
SN - 1015-6305
VL - 22
SP - 698
EP - 708
JO - Brain Pathology
JF - Brain Pathology
IS - 5
ER -