Neuroactive steroid treatment modulates myelin lipid profile in diabetic peripheral neuropathy.

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.

• Authors: Nico Mitro, Gaia Cermenati, Elisabetta Brioschi, Federico Abbiati, Matteo Audano, Silvia Giatti, Maurizio Crestani, Emma De Fabiani, Inigo Azcoitia, Luis Miguel Garcia-Segura, Donatella Caruso, Roberto Cosimo Melcangi
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 143 Pg. 115-21 (Sep 2014) ISSN: 1879-1220 [Electronic] England
• PMID: 24607810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Anabolic Agents
• Biomarkers
• Lipids
• Progestins
• RNA, Messenger
• 20-alpha-Dihydroprogesterone
• Androstane-3,17-diol

Topics

• 20-alpha-Dihydroprogesterone (pharmacology)
• Anabolic Agents (pharmacology)
• Androstane-3,17-diol (pharmacology)
• Animals
• Biomarkers (analysis)
• Chromatography, Liquid
• Diabetes Mellitus, Experimental (complications)
• Diabetic Neuropathies (drug therapy, etiology, metabolism)
• Lipids (analysis)
• Male
• Myelin Sheath (drug effects, metabolism)
• Peripheral Nervous System Diseases (drug therapy, etiology, metabolism)
• Progestins (pharmacology)
• RNA, Messenger (genetics)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Sciatic Nerve (drug effects, metabolism)
• Tandem Mass Spectrometry