RT Journal Article
T1 Neuroactive steroid treatment modulates myelin lipid profile indiabetic peripheral neuropathy
A1 Mitro, Nico
A1 Cermenati, Gaia
A1 Brioschi, Elizabetta
A1 Abbiati, Federico
A1 Audano, Matteo
A1 Giatti, Silvia
A1 Crestani, Maurizio
A1 De Fabiani, Emma
A1 Azcoitia Elías, Iñigo
A1 García-Segura, Luis Miguel
A1 Caruso, Donatella
A1 Melcangi, Roberto C.
AB 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.
PB Elsevier
SN 0960-0760, ESSN: 1879-1220
YR 2014
FD 2014-09
LK https://hdl.handle.net/20.500.14352/35630
UL https://hdl.handle.net/20.500.14352/35630
LA eng
NO Armenise Harvard Foundation Career Development (Harvard, MA, USA)
NO Fondazione Cariplo (Italia)
DS Docta Complutense
RD 6 abr 2025