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Altered expression of myelin-associated inhibitors and their receptors after traumatic brain injury in the mouse

Israelsson, Charlotte ; Flygt, Johanna ; Åstrand, Elaine ; Kiwanuka, Olivia ; Bengtsson, Henrik and Marklund, Niklas LU orcid (2014) In Restorative Neurology and Neuroscience 32(5). p.31-717
Abstract

PURPOSE: When central nervous system axons are injured, regeneration is partly inhibited by myelin-associated inhibitors (MAIs). Following traumatic brain injury (TBI) in the rat, pharmacological neutralisation of the MAIs Nogo-A and myelin-associated glycoprotein (MAG) resulted in improved functional outcome. In contrast, genetic or pharmacological neutralization of the MAI receptors Nogo-66 receptor 1 (NgR1) or paired-immunoglobulin like receptor-B (PirB) showed an unaltered or impaired outcome following TBI in mice. The aim of the present study was thus to evaluate the MAI expression levels following TBI in mice.

METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure total RNA isolated from brains of... (More)

PURPOSE: When central nervous system axons are injured, regeneration is partly inhibited by myelin-associated inhibitors (MAIs). Following traumatic brain injury (TBI) in the rat, pharmacological neutralisation of the MAIs Nogo-A and myelin-associated glycoprotein (MAG) resulted in improved functional outcome. In contrast, genetic or pharmacological neutralization of the MAI receptors Nogo-66 receptor 1 (NgR1) or paired-immunoglobulin like receptor-B (PirB) showed an unaltered or impaired outcome following TBI in mice. The aim of the present study was thus to evaluate the MAI expression levels following TBI in mice.

METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure total RNA isolated from brains of young adult male C57BL/6 mice at one, three or seven days following controlled cortical impact TBI or sham injury. Hippocampal and neocortical tissue ipsi- and contralateral to the injury was analyzed for Nogo-A, oligodendrocyte-myelin glycoprotein (OMgp), MAG, and the MAI receptors PirB and NgR1, including its co-receptor Lingo1.

RESULTS: Compared to sham-injured controls, PirB neocortical expression was significantly upregulated at one day and NgR1 expression downregulated at seven days post-TBI. In the hippocampus, transcriptional upregulation was observed in Nogo-A (one day post-injury), MAG and PirB at seven days post-injury. In contrast, the hippocampal transcripts of NgR1 and Lingo1 were decreased at seven days post-injury. The expression of OMgp was unaltered at all time points post-injury.

CONCLUSION: These results suggest that early dynamic changes in MAI gene expression occur following TBI in the mouse, particularly in the hippocampus, which may play an inhibitory role for post-injury regeneration and plasticity.

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organization
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Brain, Brain Injuries, Disease Models, Animal, GPI-Linked Proteins, Gene Expression Regulation, Male, Membrane Proteins, Mice, Mice, Inbred C57BL, Myelin Proteins, Nerve Tissue Proteins, Oligodendrocyte-Myelin Glycoprotein, RNA, Messenger, Receptors, Cell Surface, Receptors, Immunologic, Time Factors, Journal Article, Research Support, Non-U.S. Gov't
in
Restorative Neurology and Neuroscience
volume
32
issue
5
pages
31 - 717
publisher
IOS Press
external identifiers
  • scopus:84907816087
  • pmid:25079982
ISSN
1878-3627
DOI
10.3233/RNN-140419
language
English
LU publication?
no
id
c06eabde-cfc6-4e6c-9c31-51ac30d7df3d
date added to LUP
2016-12-09 16:04:57
date last changed
2024-10-05 07:56:58
@article{c06eabde-cfc6-4e6c-9c31-51ac30d7df3d,
  abstract     = {{<p>PURPOSE: When central nervous system axons are injured, regeneration is partly inhibited by myelin-associated inhibitors (MAIs). Following traumatic brain injury (TBI) in the rat, pharmacological neutralisation of the MAIs Nogo-A and myelin-associated glycoprotein (MAG) resulted in improved functional outcome. In contrast, genetic or pharmacological neutralization of the MAI receptors Nogo-66 receptor 1 (NgR1) or paired-immunoglobulin like receptor-B (PirB) showed an unaltered or impaired outcome following TBI in mice. The aim of the present study was thus to evaluate the MAI expression levels following TBI in mice.</p><p>METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure total RNA isolated from brains of young adult male C57BL/6 mice at one, three or seven days following controlled cortical impact TBI or sham injury. Hippocampal and neocortical tissue ipsi- and contralateral to the injury was analyzed for Nogo-A, oligodendrocyte-myelin glycoprotein (OMgp), MAG, and the MAI receptors PirB and NgR1, including its co-receptor Lingo1.</p><p>RESULTS: Compared to sham-injured controls, PirB neocortical expression was significantly upregulated at one day and NgR1 expression downregulated at seven days post-TBI. In the hippocampus, transcriptional upregulation was observed in Nogo-A (one day post-injury), MAG and PirB at seven days post-injury. In contrast, the hippocampal transcripts of NgR1 and Lingo1 were decreased at seven days post-injury. The expression of OMgp was unaltered at all time points post-injury.</p><p>CONCLUSION: These results suggest that early dynamic changes in MAI gene expression occur following TBI in the mouse, particularly in the hippocampus, which may play an inhibitory role for post-injury regeneration and plasticity.</p>}},
  author       = {{Israelsson, Charlotte and Flygt, Johanna and Åstrand, Elaine and Kiwanuka, Olivia and Bengtsson, Henrik and Marklund, Niklas}},
  issn         = {{1878-3627}},
  keywords     = {{Animals; Brain; Brain Injuries; Disease Models, Animal; GPI-Linked Proteins; Gene Expression Regulation; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Myelin Proteins; Nerve Tissue Proteins; Oligodendrocyte-Myelin Glycoprotein; RNA, Messenger; Receptors, Cell Surface; Receptors, Immunologic; Time Factors; Journal Article; Research Support, Non-U.S. Gov't}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{31--717}},
  publisher    = {{IOS Press}},
  series       = {{Restorative Neurology and Neuroscience}},
  title        = {{Altered expression of myelin-associated inhibitors and their receptors after traumatic brain injury in the mouse}},
  url          = {{http://dx.doi.org/10.3233/RNN-140419}},
  doi          = {{10.3233/RNN-140419}},
  volume       = {{32}},
  year         = {{2014}},
}