Neurosteroids in MS

Sabina Luchetti, MD, PhD

Steroid hormones that are produced de novo, metabolized and accumulated in the CNS are called ‘neurosteroids’. Neurosteroids are endogenous neuroprotectants, reduce inflammation and increase neuronal and glial differentiation and myelination in the CNS [1]. They may therefore influence multiple pathological aspects of MS.  In the last two years Dr. Luchetti investigated how neurosteroid synthetic pathway and hormone receptors change in Multiple sclerosis (MS) pathology [See figure].  In this study, pathway of neurosteroid synthesis and hormone receptors is analyzed by qPCR and immunohistochemistry in different lesions (e.g. chronic active, chronic inactive, remyelinating areas) and normal appearing white matter of MS patients [4].  Sex differences in neurosteroid synthesis in the MS lesions are also investigated in relation to different aspects of MS pathology such as neuroinflammation, neurodegeneration and de/remyelination processes. Alterations of neurosteroid synthetic pathway and hormone receptor are also evaluated in  MS lesion of female and male patients with different course of the disease (e.g. relapsing remitting–secondary progressive versus primary progressive MS). She recently obtained the first evidence that the neurosteroid biosynthetic pathways are indeed changed in MS tissue, and that these changes are partly gender specific [4]. These data support a key role for neurosteroids in MS pathology.

Scheme of the neurosteroid synthetic pathway

Publications

• Luchetti S, Huitinga I, Swaab DF. Neurosteroid and GABA-A receptor alterations in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Neuroscience. 2011, 19: 6-21.
• Luchetti, S, Bossers, K, Van de, BS, Agrapart, V, Morales, RR, Frajese, GV, and Swaab, DF 2011. Alterations in the histaminergic system in the substantia nigra and striatum of Parkinson’s patients: a postmortem study. Neurobiol.Aging. 32(11):1964-76
• Luchetti S, Bossers K, Frajese GV, Swaab DF. Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus in Parkinson’s disease. Brain Pathol. 2010 20(5):945-51
• Luchetti S, van Eden CG, Schuurman K, Swaab DF and Huitinga I. Sex differences in neurosteroidogenesis and hormone receptors in multiple sclerosis pathology. Submitted