Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8338671 | The Journal of Steroid Biochemistry and Molecular Biology | 2014 | 7 Pages |
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.
Keywords
ACCDPNSTZLXRstearoyl-CoA desaturase-1PMP22PROGDHPFASSCD-1ESISREBP-1c3α-diol5α-androstane-3α,17β-diolGC–MSLC–MS/MSacetyl-CoA carboxylase αinternal standardsstreptozotocinfatty acid synthasetestosteronedihydroprogesteroneSIMGas Chromatography Mass SpectrometryPeripheral nerveMetabolitesselective ion monitoringdiabetic peripheral neuropathySterol regulatory element binding protein-1cPeripheral myelin protein 22Progesteroneliquid chromatography tandem mass spectrometryAndrogen ReceptorLiver X receptorselectrospray ionization
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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,