Changes in neurosteroidogenesis during demyelination and remyelination in cuprizone-treated mice

LEICAJ ML, PASQUINI LA, LIMA A, GONZALEZ DENISELLE MC, PASQUINI JM, DE NICOLA AF, GARAY LI1,.J

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2018

0953-8194

Literature evidence indicates that changes of neurosteroids may be involved in the pathophysiologyof Multiple Sclerosis (MS). The present study assessed if changes of neurosteroidogenesis alsooccurred in gray and white matter regions of the brain from mice subjected to cuprizone-induceddemyelination. To this end, we compared the expression of neurosteroidogenic proteins includingsteroidogenic acute regulatory protein (StAR), voltage-dependent anion channel (VDAC), 18 Kdtranslocator protein (TSPO), and neurosteroidogenic enzymes including the side chain cleavageenzyme (P450scc), 3β-hydroxysteroid dehydrogenase/ isomerase (3β-HSD) and 5α-reductase (5α-R)during the demyelination and remyelination periods. Using immunohistochemistry and qPCR, wedemonstrated a decreased expression of StAR, P450scc and 5α-R in consonance with an increaseastrocytic and microglial reaction and elevated levels of TNFα during the cuprizone demyelinationperiod in hippocampus, cortex and corpus callosum. These parameters as well as the glial reactionwere normalized after two weeks of spontaneous remyelination in regions containing gray matter.Conversely, persistent elevated levels of TNFα and low levels of StAR and P450scc were observedduring remyelination in corpus callosum white matter. We concluded thatneurosteroidogenesis/myelination status and glial reactivity were inversely related in thehippocampus and neocortex. Establishing a cause and effect relationship for the measured variablesremains a future challenge to understand the pathophysiology of MS.