Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 199, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2020.105596
Keywords
Male; Female; Spinal cord; Multiple sclerosis; Pregnenolone; Cholesterol; Oxysterols
Funding
- MIUR Progetto Eccellenza
- Universita degli Studi di Milano, Italy
- Agencia Estatal de Investigacion, Spain [BFU2017-82754-R]
- Centro de Investigacion Biomedica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES)
- Instituto de Salud Carlos III, Madrid, Spain
- Fondos Feder
Ask authors/readers for more resources
Neuroactive 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available