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Title

Sex dimorphism in an animal model of multiple sclerosis: Focus on pregnenolone synthesis

AuthorsGiatti, S.; Rigolio, R.; Diviccaro, Silvia; Falvo, E.; Caruso, D.; García-Segura, Luis M. ; Cavaletti, G.; Melcangi, R.C.
KeywordsMale
Female
Spinal cord
Multiple sclerosis
Pregnenolone
Cholesterol
Oxysterols
Issue Date 17
PublisherElsevier
CitationJournal of Steroid Biochemistry and Molecular Biology 199 (2020)
AbstractNeuroactive steroids, molecules produced from cholesterol in steroidogenic cells (i.e., peripheral glands and nervous system) are physiological modulators and protective agents of nervous function. A possible role for neuroactive steroids in the sex-dimorphic clinical manifestation, onset and progression of Multiple Sclerosis (MS) has been recently suggested. To explore this possibility, we assessed the synthesis of the first steroidogenic product (pregnenolone; PREG) in the spinal cord of experimental autoimmune encephalomyelitis rats, a MS model. Data obtained indicate that the synthesis of PREG in the spinal cord is altered by the pathology in a sex-dimorphic way and depending on the pathological progression. Indeed, in male spinal cord the synthesis was already decreased at the acute phase of the disease (i.e., 14 days post induction - dpi) and maintained low during the chronic phase (i.e., 45 dpi), while in females this effect was observed only at the chronic phase. Substrate availability had also a role in the sex-dimorphic kinetics. Indeed, at the chronic phase, male animals showed a reduction in the levels of free cholesterol coupled to alteration of cholesterol metabolism into oxysterols; these effects were not observed in female animals. These findings suggest that the comprehension of the neurosteroidogenic processes could be relevant to better understand the sexual dimorphism of MS and to possibly design sex-oriented therapeutic strategies based on neuroactive steroids.
Publisher version (URL)http://dx.doi.org/10.1016/j.jsbmb.2020.105596
URIhttp://hdl.handle.net/10261/228361
Identifiersdoi: 10.1016/j.jsbmb.2020.105596
issn: 1879-1220
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