Advanced

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 (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.

(Less)
Please use this url to cite or link to this publication:
author
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
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
2017-08-13 05:01:48
@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},
  keyword      = {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},
  volume       = {32},
  year         = {2014},
}