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Neuroactive steroid treatment modulates myelin lipid profile in diabetic peripheral neuropathy
- Source :
- The Journal of Steroid Biochemistry and Molecular Biology. 143:115-121
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Diabetic peripheral neuropathy causes a decrease in the levels of dihydroprogesterone and 5α-androstane-3α,17β-diol (3α-diol) in the peripheral nerves. These two neuroactive steroids exert protective effects, by mechanisms that still remain elusive. We have previously shown that the activation of Liver X Receptors improves the peripheral neuropathic phenotype in diabetic rats. This protective effect is accompanied by the restoration to control values of the levels of dihydroprogesterone and 3α-diol in peripheral nerves. In addition, activation of these receptors decreases peripheral myelin abnormalities by improving the lipid desaturation capacity, which is strongly blunted by diabetes, and ultimately restores the myelin lipid profile to non-diabetic values. On this basis, we here investigate whether dihydroprogesterone or 3α-diol may exert their protective effects by modulating the myelin lipid profile. We report that both neuroactive steroids act on the lipogenic gene expression profile in the sciatic nerve of diabetic rats, reducing the accumulation of myelin saturated fatty acids and promoting desaturation. These changes were associated with a reduction in myelin structural alterations. These findings provide evidence that dihydroprogesterone and 3α-diol are protective agents against diabetic peripheral neuropathy by regulating the de novo lipogenesis pathway, which positively influences myelin lipid profile.
- Subjects :
- Male
medicine.medical_specialty
Neuroactive steroid
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Real-Time Polymerase Chain Reaction
Biochemistry
Diabetes Mellitus, Experimental
Rats, Sprague-Dawley
Myelin
Anabolic Agents
Endocrinology
Diabetic Neuropathies
Tandem Mass Spectrometry
Diabetes mellitus
Internal medicine
medicine
Animals
RNA, Messenger
Liver X receptor
Molecular Biology
Myelin Sheath
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
Chemistry
Peripheral Nervous System Diseases
Cell Biology
medicine.disease
Androstane-3,17-diol
Lipids
Sciatic Nerve
20-alpha-Dihydroprogesterone
Rats
medicine.anatomical_structure
Peripheral neuropathy
Dihydroprogesterone
Lipogenesis
Molecular Medicine
Progestins
Lipid profile
Biomarkers
Chromatography, Liquid
Subjects
Details
- ISSN :
- 09600760
- Volume :
- 143
- Database :
- OpenAIRE
- Journal :
- The Journal of Steroid Biochemistry and Molecular Biology
- Accession number :
- edsair.doi.dedup.....96768c04ff2013fda512d7fea3ae794a