Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β
<p>Abstract</p> <p>Background</p> <p>Animals respond to inflammation by suppressing normal high-energy activities, including feeding and locomotion, in favor of diverting resources to the immune response. The cytokine interleukin-1 beta (IL-1β) inhibits normal feeding a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-10-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/9/1/229 |
| _version_ | 1818135955665584128 |
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| author | Braun Theodore P Grossberg Aaron J Veleva-Rotse Biliana O Maxson Julia E Szumowski Marek Barnes Anthony P Marks Daniel L |
| author_facet | Braun Theodore P Grossberg Aaron J Veleva-Rotse Biliana O Maxson Julia E Szumowski Marek Barnes Anthony P Marks Daniel L |
| author_sort | Braun Theodore P |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Animals respond to inflammation by suppressing normal high-energy activities, including feeding and locomotion, in favor of diverting resources to the immune response. The cytokine interleukin-1 beta (IL-1β) inhibits normal feeding and locomotor activity (LMA) via its actions in the central nervous system (CNS). Behavioral changes in response to IL-1β are mediated by myeloid differentiation factor 88 (MyD88) in non-hematopoietic cells. It is unknown whether IL-1β acts directly on neurons or requires transduction by non-neuronal cells.</p> <p>Methods</p> <p>The Nestin-cre mouse was crossed with MyD88<sup>lox</sup> mice to delete MyD88 from neurons and glia in the CNS (MyD88<sup>ΔCNS</sup>). These mice were compared to total body MyD88KO and wild type (WT) mice. Mice had cannulae stereotactically placed in the lateral ventricle and telemetry transponders implanted into the peritoneum. Mice were treated with either intracerebroventricular (i.c.v.) IL-1β (10 ng) or vehicle. Food intake, body weight and LMA were continuously monitored for 24 h after treatment. I.c.v. tumor necrosis factor (TNF), a MyD88-independent cytokine, was used to control for normal immune development. Peripheral inflammation was modeled using intraperitoneal lipopolysaccharide (LPS). Groups were compared using two-way ANOVA with Bonferroni post-test. Efficacy of recombination was evaluated using tdTomato reporter mice crossed with the Nestin-cre mouse. MyD88 deletion was confirmed by Western blot.</p> <p>Results</p> <p>I.c.v. IL-1β treatment caused a significant reduction in feeding, body weight and LMA in WT mice. MyD88KO mice were protected from these changes in response to i.c.v. IL-1β despite having intact behavioral responses to TNF. Cre-mediated recombination was observed in neurons and astrocytes, but not microglia or endothelial cells. In contrast to MyD88KO mice, the behavioral responses of MyD88<sup>ΔCNS</sup> mice to i.c.v. IL-1β or intraperitoneal (i.p.) LPS were indistinguishable from those of WT mice.</p> <p>Conclusion</p> <p>Sickness behavior is mediated by MyD88 and is dependent on the activity of cytokines within the brain. Our results demonstrate that MyD88 is not required in neurons or astrocytes to induce this behavioral response to IL-1β or LPS. This suggests that a non-<it>Nestin</it> expressing cell population responds to IL-1β in the CNS and transduces the signal to neurons controlling feeding and activity.</p> |
| first_indexed | 2024-12-11T09:32:44Z |
| format | Article |
| id | doaj.art-2d5c134a818f41d49a444285f0be7f69 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-11T09:32:44Z |
| publishDate | 2012-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-2d5c134a818f41d49a444285f0be7f692022-12-22T01:12:58ZengBMCJournal of Neuroinflammation1742-20942012-10-019122910.1186/1742-2094-9-229Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1βBraun Theodore PGrossberg Aaron JVeleva-Rotse Biliana OMaxson Julia ESzumowski MarekBarnes Anthony PMarks Daniel L<p>Abstract</p> <p>Background</p> <p>Animals respond to inflammation by suppressing normal high-energy activities, including feeding and locomotion, in favor of diverting resources to the immune response. The cytokine interleukin-1 beta (IL-1β) inhibits normal feeding and locomotor activity (LMA) via its actions in the central nervous system (CNS). Behavioral changes in response to IL-1β are mediated by myeloid differentiation factor 88 (MyD88) in non-hematopoietic cells. It is unknown whether IL-1β acts directly on neurons or requires transduction by non-neuronal cells.</p> <p>Methods</p> <p>The Nestin-cre mouse was crossed with MyD88<sup>lox</sup> mice to delete MyD88 from neurons and glia in the CNS (MyD88<sup>ΔCNS</sup>). These mice were compared to total body MyD88KO and wild type (WT) mice. Mice had cannulae stereotactically placed in the lateral ventricle and telemetry transponders implanted into the peritoneum. Mice were treated with either intracerebroventricular (i.c.v.) IL-1β (10 ng) or vehicle. Food intake, body weight and LMA were continuously monitored for 24 h after treatment. I.c.v. tumor necrosis factor (TNF), a MyD88-independent cytokine, was used to control for normal immune development. Peripheral inflammation was modeled using intraperitoneal lipopolysaccharide (LPS). Groups were compared using two-way ANOVA with Bonferroni post-test. Efficacy of recombination was evaluated using tdTomato reporter mice crossed with the Nestin-cre mouse. MyD88 deletion was confirmed by Western blot.</p> <p>Results</p> <p>I.c.v. IL-1β treatment caused a significant reduction in feeding, body weight and LMA in WT mice. MyD88KO mice were protected from these changes in response to i.c.v. IL-1β despite having intact behavioral responses to TNF. Cre-mediated recombination was observed in neurons and astrocytes, but not microglia or endothelial cells. In contrast to MyD88KO mice, the behavioral responses of MyD88<sup>ΔCNS</sup> mice to i.c.v. IL-1β or intraperitoneal (i.p.) LPS were indistinguishable from those of WT mice.</p> <p>Conclusion</p> <p>Sickness behavior is mediated by MyD88 and is dependent on the activity of cytokines within the brain. Our results demonstrate that MyD88 is not required in neurons or astrocytes to induce this behavioral response to IL-1β or LPS. This suggests that a non-<it>Nestin</it> expressing cell population responds to IL-1β in the CNS and transduces the signal to neurons controlling feeding and activity.</p>http://www.jneuroinflammation.com/content/9/1/229Sickness behaviorMyD88CytokinesInflammationHypothalamusIL-1βCachexiaLethargy |
| spellingShingle | Braun Theodore P Grossberg Aaron J Veleva-Rotse Biliana O Maxson Julia E Szumowski Marek Barnes Anthony P Marks Daniel L Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β Journal of Neuroinflammation Sickness behavior MyD88 Cytokines Inflammation Hypothalamus IL-1β Cachexia Lethargy |
| title | Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β |
| title_full | Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β |
| title_fullStr | Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β |
| title_full_unstemmed | Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β |
| title_short | Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β |
| title_sort | expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin 1β |
| topic | Sickness behavior MyD88 Cytokines Inflammation Hypothalamus IL-1β Cachexia Lethargy |
| url | http://www.jneuroinflammation.com/content/9/1/229 |
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