| Title |
Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS
|
|---|---|
| Published in |
Acta Neuropathologica, August 2012
|
| DOI | 10.1007/s00401-012-1034-0 |
| Pubmed ID | |
| Authors |
Jigisha R. Patel, Jessica L. Williams, Megan M. Muccigrosso, Laindy Liu, Tao Sun, Joshua B. Rubin, Robyn S. Klein |
| Abstract |
Multiple sclerosis (MS) is characterized by episodes of inflammatory demyelination with progressive failure of remyelination. Prior studies using murine models of MS indicate that remyelination within the adult central nervous system (CNS) requires the expression and activity of TNFR2 and CXCR4 by oligodendrocyte progenitor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes. Here, we extend these studies by examining the role of TNFR2 in the expression of the CXCR4 ligand, CXCL12, within the corpus callosum (CC) during cuprizone (CPZ) intoxication and by demonstrating that lentiviral-mediated gene delivery of CXCL12 to the demyelinated CC improves OPC proliferation and myelin expression during remyelination. Activated astrocytes and microglia express both TNFR1 and TNFR2 within the demyelinated CC. However, CPZ intoxicated TNFR2-/- mice exhibit loss of up-regulation of CXCL12 in astrocytes with concomitant decreases in numbers of CXCR4+ NG2+ OPCs within the CC. While CXCR4 antagonism does not affect OPC migration from subventricular zones into the CC, it decreases their proliferation and differentiation within the CC. Stereotactic delivery of lentivirus expressing CXCL12 protein into the CC of acutely demyelinated TNFR2-/- mice increases OPC proliferation and expression of myelin. In contrast, chronically demyelinated wild-type mice, which exhibit significant loss of astrocytes and OPCs, are unable to be rescued via CXCL12 lentivirus alone but instead required engraftment of CXCL12-expressing astrocytes for increased myelin expression. Our results show that TNFR2 activation induces CXCL12 expression in the demyelinated CC via autocrine signaling specifically within astrocytes, which promotes OPC proliferation and differentiation. In addition, gene delivery of critical pro-myelinating proteins might be a feasible approach for the treatment of remyelination failure in MS. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 103 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | <1% |
| Japan | 1 | <1% |
| China | 1 | <1% |
| Unknown | 100 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 27 | 26% |
| Researcher | 16 | 16% |
| Student > Bachelor | 16 | 16% |
| Student > Master | 11 | 11% |
| Student > Doctoral Student | 5 | 5% |
| Other | 15 | 15% |
| Unknown | 13 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 32 | 31% |
| Neuroscience | 20 | 19% |
| Medicine and Dentistry | 16 | 16% |
| Biochemistry, Genetics and Molecular Biology | 9 | 9% |
| Immunology and Microbiology | 4 | 4% |
| Other | 6 | 6% |
| Unknown | 16 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 November 2012.
All research outputs
#18,319,742
of 22,684,168 outputs
Outputs from Acta Neuropathologica
#2,193
of 2,359 outputs
Outputs of similar age
#130,018
of 169,692 outputs
Outputs of similar age from Acta Neuropathologica
#21
of 24 outputs
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