Neuroactive steroid treatment modulates myelin lipid profile indiabetic peripheral neuropathy



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Mitro, Nico and Cermenati, Gaia and Brioschi, Elizabetta and Abbiati, Federico and Audano, Matteo and Giatti, Silvia and Crestani, Maurizio and De Fabiani, Emma and Azcoitia Elías, Iñigo and García-Segura, Luis Miguel and Caruso, Donatella and Melcangi, Roberto C. (2014) Neuroactive steroid treatment modulates myelin lipid profile indiabetic peripheral neuropathy. Journal of Steroid Biochemistry and Molecular Biology, 143 . pp. 115-121. ISSN 0960-0760, ESSN: 1879-1220

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Diabetic peripheral neuropathy causes a decrease in the levels of dihydroprogesterone and 5- androstane-3,17-diol (3-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 3-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 3-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 3-diol are protective agents against diabetic peripheral neuropathy by regulating the de novo lipogenesis pathway, which positively influences myelin lipid profile.

Item Type:Article
Uncontrolled Keywords:Progesterone; Testosterone; Metabolites; Streptozotocin; Peripheral nerve
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Neurosciences
ID Code:47742
Deposited On:25 May 2018 11:23
Last Modified:28 May 2018 07:05

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