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Neuronal LXR Regulates Neuregulin-1 Expression and Sciatic Nerve-Associated Cell signaling
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- Neuropathic pain caused by peripheral nerve injury significantly affects sensory perception and quality of life. Accumulating evidence strongly link cholesterol and inflammation with development and progression of Obesity and Diabetes associated-neuropathies. However, the exact mechanisms of how lipid metabolism in peripheral nervous system (PNS) contributes to the pathogenesis of neuropathy remains poorly understood. Dysregulation of LXR pathways have been identified in many transcriptomic analyses in neuropathy models. LXR α/β expressed in sensory neurons are necessary for proper peripheral nerve function. Deletion of LXR α/β from sensory neurons lead to pain-like behaviors. In this study, we identified that LXR α/β expressed in sensory neurons regulates neuronal neuregulin-1 (Nrg1). Using in vivo cell-specific approaches, we observed that loss of LXR from sensory neurons altered genes regulating lipid metabolism in non-neuronal cells potentially representing Schwann cells (SC). Our data suggest that neuronal LXR may regulates SC function via a Nrg1-dependent mechanism. The decrease in Nrg1 expression in DRG neurons of WD-fed mice may suggest an altered Nrg1-dependent neuron-SC communication in Obesity. The communication between neurons and non-neuronal cell such as SC could be a new biological pathway to study and to treat Obesity-associated neuropathy and PNS dysfunction.
- Subjects :
- 0303 health sciences
Cell signaling
biology
Inflammation
Lipid metabolism
03 medical and health sciences
0302 clinical medicine
medicine.anatomical_structure
nervous system
Peripheral nervous system
Peripheral nerve injury
biology.protein
medicine
lipids (amino acids, peptides, and proteins)
Sciatic nerve
Neuregulin 1
medicine.symptom
Liver X receptor
Neuroscience
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....02bb08b1e6bf23c9ad030ec1a64080bc
- Full Text :
- https://doi.org/10.1101/2020.01.14.907048