Neuroactive steroid levels are altered in several experimental models of peripheral neuropathy, and on this basis, they have been proposed as protective agents. For the first time, the levels of these molecules were here assessed in sterol regulatory-binding protein-1c (SREBP-1c) knock-out (KO) male mice (i.e., an experimental model of peripheral neuropathy) and compared with observations in wild type animals. The levels of neuroactive steroids have been evaluated by liquid chromatography tandem mass spectrometry in plasma and sciatic nerve at two and ten months of age and these analyses were implemented analyzing the gene expression of crucial steroidogenic enzymes in sciatic nerve. Data obtained at two months of age showed high levels of pregnenolone in sciatic nerve, associated with low levels of its first metabolite, progesterone, and further metabolites (i.e., 5α-pregnane-3,20-dione and 5α-pregnan-3β-ol-20-one). High levels of testosterone and 17β-estradiol were also observed. At ten months of age, the neuroactive steroid profile showed some differences. Indeed, low levels of pregnenolone and high levels of 5α-pregnan-3α-ol-20-one and 5α-pregnan-3β-ol-20-one were observed. The analysis of the gene expression of steroidogenic enzymes here considered generally followed these changes. Interestingly, the levels of pregnenolone and progesterone were unmodified in plasma suggesting a specific effect of SREBP-1c on neurosteroidogenesis. Because this peripheral neuropathy is due to altered fatty acid biosynthesis, data here reported support the belief that the cross-talk between this biosynthetic pathway and neuroactive steroids may represent a possible therapeutic strategy for peripheral neuropathy. This article is protected by copyright. All rights reserved.
Sterol regulatory element binding protein-1c Knockout mice show altered neuroactive steroid levels in sciatic nerve / N. Mitro, G. Cermenati, M. Audano, S. Giatti, M. Pesaresi, S. Pedretti, R. Spezzano, D. Caruso, R.C. Melcangi. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 142:3(2017 Aug), pp. 420-428.
|Titolo:||Sterol regulatory element binding protein-1c Knockout mice show altered neuroactive steroid levels in sciatic nerve|
MITRO, NICO (Primo)
CERMENATI, GAIA (Secondo)
CARUSO, DONATELLA (Penultimo)
|Parole Chiave:||fatty acid biosynthesis; liquid chromatography-tandem mass spectrometry; neurosteroids; pregnenolone; progesterone metabolites; testosterone metabolites|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
Settore BIO/10 - Biochimica
|Data di pubblicazione:||ago-2017|
|Data ahead of print / Data di stampa:||29-mag-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/jnc.14063|
|Appare nelle tipologie:||01 - Articolo su periodico|
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