PMID- 24607810
OWN - NLM
STAT- MEDLINE
DCOM- 20141229
LR  - 20220311
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 143
DP  - 2014 Sep
TI  - Neuroactive steroid treatment modulates myelin lipid profile in diabetic 
      peripheral neuropathy.
PG  - 115-21
LID - S0960-0760(14)00044-2 [pii]
LID - 10.1016/j.jsbmb.2014.02.015 [doi]
AB  - Diabetic peripheral neuropathy causes a decrease in the levels of 
      dihydroprogesterone and 5alpha-androstane-3alpha,17beta-diol (3alpha-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 3alpha-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 3alpha-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 3alpha-diol are protective agents against diabetic peripheral 
      neuropathy by regulating the de novo lipogenesis pathway, which positively 
      influences myelin lipid profile.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Mitro, Nico
AU  - Mitro N
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - Cermenati, Gaia
AU  - Cermenati G
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - Brioschi, Elisabetta
AU  - Brioschi E
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - Abbiati, Federico
AU  - Abbiati F
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - Audano, Matteo
AU  - Audano M
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - Giatti, Silvia
AU  - Giatti S
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - Crestani, Maurizio
AU  - Crestani M
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - De Fabiani, Emma
AU  - De Fabiani E
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy.
FAU - Azcoitia, Inigo
AU  - Azcoitia I
AD  - Departamento de Biologia Celular, Facultad de Biologia, Universidad Complutense 
      de Madrid, E-28040 Madrid, Spain.
FAU - Garcia-Segura, Luis Miguel
AU  - Garcia-Segura LM
AD  - Instituto Cajal, C.S.I.C., E-28002 Madrid, Spain.
FAU - Caruso, Donatella
AU  - Caruso D
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy. Electronic address: 
      donatella.caruso@unimi.it.
FAU - Melcangi, Roberto Cosimo
AU  - Melcangi RC
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, via Balzaretti 9, 20133 Milan, Italy. Electronic address: 
      roberto.melcangi@unimi.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140304
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Anabolic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Lipids)
RN  - 0 (Progestins)
RN  - 0 (RNA, Messenger)
RN  - 145-14-2 (20-alpha-Dihydroprogesterone)
RN  - 25126-76-5 (Androstane-3,17-diol)
SB  - IM
MH  - 20-alpha-Dihydroprogesterone/*pharmacology
MH  - Anabolic Agents/pharmacology
MH  - Androstane-3,17-diol/*pharmacology
MH  - Animals
MH  - Biomarkers/analysis
MH  - Chromatography, Liquid
MH  - Diabetes Mellitus, Experimental/complications
MH  - Diabetic Neuropathies/drug therapy/etiology/*metabolism
MH  - Lipids/*analysis
MH  - Male
MH  - Myelin Sheath/drug effects/*metabolism
MH  - Peripheral Nervous System Diseases/drug therapy/etiology/*metabolism
MH  - Progestins/pharmacology
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sciatic Nerve/drug effects/*metabolism
MH  - Tandem Mass Spectrometry
OTO - NOTNLM
OT  - Metabolites
OT  - Peripheral nerve
OT  - Progesterone
OT  - Streptozotocin
OT  - Testosterone
EDAT- 2014/03/13 06:00
MHDA- 2014/12/30 06:00
CRDT- 2014/03/11 06:00
PHST- 2014/01/02 00:00 [received]
PHST- 2014/02/19 00:00 [revised]
PHST- 2014/02/22 00:00 [accepted]
PHST- 2014/03/11 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
AID - S0960-0760(14)00044-2 [pii]
AID - 10.1016/j.jsbmb.2014.02.015 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2014 Sep;143:115-21. doi: 
      10.1016/j.jsbmb.2014.02.015. Epub 2014 Mar 4.