Sex steroids, neurosteroidogenesis, and inflammation in multiple sclerosis and related animal models

GARAY L; MEYER M; GUENNOUN R; SCHUMACHER, M; GONZALEZ DENISELLE MC; DE NICOLA A. F.

Current Opinion in Endocrine and Metabolic Research

Elsevier

Año: 2021

2451-9650

Multiple sclerosis (MS) and rodent models of the diseaseincluding experimental autoimmune encephalomyelitis, cupri-zone intoxication, and lysophosphatidyl choline-induced demye-lination show altered levels of circulating sex steroids andchanges in the biosynthesis of nervous system localized ste-roidogenesis (neurosteroidogenesis). Therapy with progester-one, estrogens, androgens, or direct stimulation ofneurosteroidogenesis shows beneficial effects for brain andspinal cord neuropathology of MS models owing to the reductionof reactive astrocytes and microglia, downregulation of theexpression of proinflammatory markers, improved myelin forma-tion from oligodendrocyte precursors, and better clinical scoresand behavioral performances. Steroid effectiveness is explainedin part by activation of classical nuclear receptors, membranereceptors, and modulation of gamma aminobutyric acid (GABAA)receptors expressed by several cell types from different centralnervous system (CNS) regions. Because resolving inflammationis crucial for treatment of MS and related animal models, treat-ment with natural or synthetic steroidsor with molecules targetingneurosteroidogenesismayopenfurther therapeuticopportunitiesfor neuroinflammatory diseases