| Autor: |
Bastien, Dominic, Landete, Victor Bellver, Lessard, Martine, Vallières, Nicolas, Champagne, Mathieu, Takashima, Akira, Tremblay, Marie-Ève, Doyon, Yannick, Lacroix, Steve |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 7/29/2015, Vol. 35 Issue 30, p10715-10730, 16p |
| Abstrakt: |
Spinal cord injury (SCI) causes the release of danger signals by stressed and dying cells, a process that leads to neuroinflammation. Evidence suggests that inflammation plays a role in both the damage and repair of injured neural tissue. We show that microglia at sites of SCI rapidly express the alarmin interleukin (IL)-1α, and that infiltrating neutrophils and macrophages subsequently produce IL-1β. Infiltration of these cells is dramatically reduced in both IL-1α-/- and IL-1β-/- mice, but only IL-1α-/- mice showed rapid (at day 1) and persistent improvements in locomotion associated with reduced lesion volume. Similarly, intrathecal administration of the IL-1 receptor antagonist anakinra restored locomotor function post-SCI. Transcriptome analysis of SCI tissue at day 1 identified the survival factor Tox3 as being differentially regulated exclusively in IL-1α-/- mice compared with IL-1β-/- and wild-type mice. Accordingly, IL-1α-/- mice have markedly increased Tox3 levels in their oligodendrocytes, beginning at postnatal day 10 (P10) and persisting through adulthood. At P10, the spinal cord of IL-1α-/- mice showed a transient increase in mature oligodendrocyte numbers, coinciding with increased IL-1α expression in wild-type animals. In adult mice, IL-1α deletion is accompanied by increased oligodendrocyte survival after SCI. TOX3 overexpression in human oligodendrocytes reduced cellular death under conditions mimicking SCI. These results suggest that IL-1α-mediated Tox3 suppression during the early phase of CNS insult plays a crucial role in secondary degeneration. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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