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MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation
Abstract
Activation of neuronal circuits involved in the control of autonomic responses is critical for the host survival to immune threats. The brain vascular system plays a key role in such immune-CNS communication, but the signaling pathway and exact type of cells within the blood-brain barrier (BBB) mediating these functions have yet to be uncovered. To elucidate this issue we used myeloid differentiation factor 88 (MyD88)-deficient mice, because these animals do not show any responses to the cytokine interleukin-1beta (IL-1beta). We created chimeric mice with competent MyD88 signaling in either the BBB endothelium or perivascular microglia of bone marrow origin and challenged them with IL-1beta. Systemic treatment with the cytokine caused a robust transcriptional activation of genes involved in the prostaglandin E(2) (PGE(2)) production by vascular cells of the brain. Upregulation of these genes is dependent on a functional MyD88 signaling in the endothelium, because MyD88-deficient mice that received bone marrow stem cells from wild-type animals (for example, functional perivascular microglia) exhibited no response to systemic IL-1beta administration. MyD88 competent endothelial cells also mediate neuronal activation and plasma release of glucocorticoids, whereas chimeric mice with MyD88-competent perivascular microglia did not show a significant increase of these functions. Moreover, competent endothelial cells for the gene encoding Toll-like receptor 4 (TLR4) are essential for…
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“In TLR4 transgenic mice, activation of the HPA axis in response to Gram-negative bacteria is absent (Gosselin and Rivest, 2008).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gosselin and Rivest, 2008
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Metadata
- Authors
- Gosselin, D., & Rivest, S.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Rivest, S
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2008-01-08
- Volume
- 13
- Issue
- 5
- Pages
- 480-497
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2054606341
- Cited by
- 109
- References
- 52
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 10 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 9 · 2012: 9
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research
- Canada Research Chairs
- Max-Planck-Gesellschaft
- National Institutes of Health
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- MyD88 signaling, brain endothelial cells, blood-brain barrier, systemic inflammation, IL-1β, corticosterone, neuronal activation, perivascular microglia, TLR4, prostaglandin E2, chimeric mice, bone marrow transplantation, lipopolysaccharide
- MeSH terms
- Prostaglandin-E Synthases, Animals, Blood-Brain Barrier, Bone Marrow Cells, Brain, Corticosterone, Inflammation, Mice, Inbred C3H, Mice, Inbred C57BL, Dinoprostone, Signal Transduction, Bone Marrow Transplantation, Microglia, Transplantation Chimera, Mice, Knockout, Inflammation Mediators, Intramolecular Oxidoreductases, Endothelial Cells, Toll-Like Receptor 4, Mice, Cyclooxygenase 2, Interleukin-1beta, Myeloid Differentiation Factor 88
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