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

Publication date: Available online 17 January 2020Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): S. Giatti, R. Rigolio, S. Diviccaro, E. Falvo, D. Caruso, L.M. Garcia-Segura, G. Cavaletti, R.C. MelcangiABSTRACTNeuroactive 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 an...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research