Cholesterol-dependent LXR transcription factor activity represses pronociceptive effects of estrogen in sensory neurons and pain induced by myelin basic protein fragments.
Cholesterol
DRG culture
Estrogen
Interleukin 6
LXR
Liver x receptor
Myelin basic protein
Neuropathic pain
Oxysterol
Sensory neuron
Journal
Brain, behavior, & immunity - health
ISSN: 2666-3546
Titre abrégé: Brain Behav Immun Health
Pays: United States
ID NLM: 101759062
Informations de publication
Date de publication:
Jul 2024
Jul 2024
Historique:
received:
11
03
2024
accepted:
17
03
2024
medline:
9
4
2024
pubmed:
9
4
2024
entrez:
9
4
2024
Statut:
epublish
Résumé
A bioactive myelin basic protein (MBP) fragment, comprising MBP In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP CCI regulated LXRα ligand and receptor levels in nerves of both sexes, with cholesterol precursors, desmosterol and 7-DHC, and oxysterol elevated in females relative to males. MBP The injury-released bioactive MBP fragments induce pronociceptive changes by selective inactivation of nuclear transcription factors, including LXRα. By Ncoa1 sequestration, bioactive MBP fragments render LXRα function to counteract pronociceptive activity of estrogen/ESR1 in sensory neurons. This effect of MBP fragments is prevalent in females due to high circulating estrogen levels in females relative to males. Restoring LXR activity presents a promising therapeutic strategy in management of neuropathic pain induced by bioactive MBP.
Sections du résumé
Background
UNASSIGNED
A bioactive myelin basic protein (MBP) fragment, comprising MBP
Methods
UNASSIGNED
In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP
Results
UNASSIGNED
CCI regulated LXRα ligand and receptor levels in nerves of both sexes, with cholesterol precursors, desmosterol and 7-DHC, and oxysterol elevated in females relative to males. MBP
Conclusion
UNASSIGNED
The injury-released bioactive MBP fragments induce pronociceptive changes by selective inactivation of nuclear transcription factors, including LXRα. By Ncoa1 sequestration, bioactive MBP fragments render LXRα function to counteract pronociceptive activity of estrogen/ESR1 in sensory neurons. This effect of MBP fragments is prevalent in females due to high circulating estrogen levels in females relative to males. Restoring LXR activity presents a promising therapeutic strategy in management of neuropathic pain induced by bioactive MBP.
Identifiants
pubmed: 38590761
doi: 10.1016/j.bbih.2024.100757
pii: S2666-3546(24)00035-8
pmc: PMC10999831
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100757Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.