Cholesterol-dependent LXR transcription factor activity represses pronociceptive effects of estrogen in sensory neurons and pain induced by myelin basic protein fragments.

ABSTRACT:

Background

A bioactive myelin basic protein (MBP) fragment, comprising MBP_84-104, is released in sciatic nerve after chronic constriction injury (CCI). Intraneural injection (IN) of MBP_84-104 in an intact sciatic nerve is sufficient to induce persistent neuropathic pain-like behavior via robust transcriptional remodeling at the injection site and ipsilateral dorsal root ganglia (DRG) and spinal cord. The sex (female)-specific pronociceptive activity of MBP_84-104 associates with sex-specific changes in cholesterol metabolism and activation of estrogen receptor (ESR)1 signaling.

Methods

In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP_84-104

SUBMITTER: Hullugundi SK 

PROVIDER: S-EPMC10999831 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature