Does vagal TLR4 cause LPS anorexia—or mainly CGRP release?
Restoring TLR4 only in Nav1.8 afferents did not restore LPS anorexia, but LPS still triggered CGRP release from TLR4+/CGRP+ vagal jugular neurons.
Source
TLR4 Signaling Selectively and Directly Promotes CGRP Release from Vagal Afferents in the Mouse
What they did
Built Tlr4 LoxTB mice, restored TLR4 globally (Zp3-Cre) or in Nav1.8 afferents, mapped Tlr4 with ISH, and applied LPS to cultured afferents.
What they found
Nav1.8-restricted TLR4 was insufficient for rapid-onset LPS anorexia; Tlr4 enriched in jugular Nav1.8/CGRP vagal afferents; LPS stimulated CGRP release in vitro.
The limits
What it doesn't show
Does not map the full in vivo infection-fighting role of the LPS–TLR4–CGRP loop or test female experimental cohorts for feeding assays.
Key terms
- TLR4
- Innate immune receptor that senses bacterial LPS.
- LPS
- Lipopolysaccharide from Gram-negative bacteria.
- CGRP
- Calcitonin gene-related peptide released from sensory afferents.
- Nav1.8 afferents
- Peripheral sensory neurons expressing the Nav1.8 sodium channel.
- Tlr4 LoxTB
- Mouse with a loxP-flanked transcription blocker silencing Tlr4 until Cre removal.
- Jugular ganglion
- Vagal sensory ganglion enriched for Tlr4/CGRP neurons here.
Flashcards
Research intelligence for this paper
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Quiz yourself
Nav1.8-restricted TLR4 restored LPS anorexia?
Common questions
Did Nav1.8-TLR4 restore anorexia?
No—LPS did not cause rapid-onset anorexia.
What did LPS trigger?
CGRP release from cultured Nav1.8-restricted TLR4 afferents.
Where is Tlr4 enriched?
Jugular vagal Nav1.8 afferents co-expressing CGRP.
New tool?
Cre-reactivatable Tlr4 LoxTB mouse.