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Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

Rasmussen, Stine LU ; Wang, Yue; Kivisakk, Pia; Bronson, Roderick T; Meyer, Morten; Imitola, Jaime and Khoury, Samia J (2007) In Brain 130(11). p.2816-2829
Abstract
Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar to lesions found in MS. Unlike the T-cell infiltrates that peak during acute disease, we found that microglia activation persists through the chronic disease phase. Microglia activation correlated with abnormal phosphorylation of neurofilaments in the cortex and stripping of synaptic proteins in cortical callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in... (More)
Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar to lesions found in MS. Unlike the T-cell infiltrates that peak during acute disease, we found that microglia activation persists through the chronic disease phase. Microglia activation correlated with abnormal phosphorylation of neurofilaments in the cortex and stripping of synaptic proteins in cortical callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in the labelling of their transcallosal axons. These data demonstrate a novel paradigm of cortical and callosal neuropathology in a mouse model of MS, perpetuated by innate immunity. These features closely mimic the periventricular and cortical pathology described in MS patients and establish a model that could be useful to study mechanisms of progression in MS. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Brain
volume
130
issue
11
pages
2816 - 2829
publisher
Oxford University Press
external identifiers
  • scopus:35649010838
ISSN
1460-2156
DOI
10.1093/brain/awm219
language
English
LU publication?
no
id
665f7af9-b39f-4dc9-86a0-9183c39d7f54 (old id 1299052)
date added to LUP
2009-07-09 14:37:09
date last changed
2017-11-19 03:38:33
@article{665f7af9-b39f-4dc9-86a0-9183c39d7f54,
  abstract     = {Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar to lesions found in MS. Unlike the T-cell infiltrates that peak during acute disease, we found that microglia activation persists through the chronic disease phase. Microglia activation correlated with abnormal phosphorylation of neurofilaments in the cortex and stripping of synaptic proteins in cortical callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in the labelling of their transcallosal axons. These data demonstrate a novel paradigm of cortical and callosal neuropathology in a mouse model of MS, perpetuated by innate immunity. These features closely mimic the periventricular and cortical pathology described in MS patients and establish a model that could be useful to study mechanisms of progression in MS.},
  author       = {Rasmussen, Stine and Wang, Yue and Kivisakk, Pia and Bronson, Roderick T and Meyer, Morten and Imitola, Jaime and Khoury, Samia J},
  issn         = {1460-2156},
  language     = {eng},
  number       = {11},
  pages        = {2816--2829},
  publisher    = {Oxford University Press},
  series       = {Brain},
  title        = {Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis},
  url          = {http://dx.doi.org/10.1093/brain/awm219},
  volume       = {130},
  year         = {2007},
}