Student and Faculty Publications
Publication Date
7-1-2024
Journal
Brain, Behavior, & Immunity - Health
Abstract
BACKGROUND: A bioactive myelin basic protein (MBP) fragment, comprising MBP
METHODS: In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP
RESULTS: 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: 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.
Keywords
Neuropathic pain, Oxysterol, Cholesterol, Liver x receptor, LXR, Myelin basic protein, Estrogen, Interleukin 6, DRG culture, Sensory neuron
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Bioinformatics Commons, Biomedical Informatics Commons, Internal Medicine Commons, Neurology Commons, Neurosciences Commons
Comments
Supplementary Materials
PMID: 38590761