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
Inspect source passages
Does vagal TLR4 cause LPS anorexia—or mainly CGRP release?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Nav1.8-restricted TLR4 insufficient for LPS rapid-onset anorexia.
Contrary to our expectations, the administration of LPS did not cause rapid-onset anorexia in mice with Na v 1.8-restricted TLR4
LPS sufficient to stimulate CGRP release in vitro.
the application of LPS to cultured Na v 1.8-restricted TLR4 afferents was sufficient to stimulate the release of CGRP
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
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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.