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

LEICAJ ML,PASQUINI LA, LIMA A, GONZALEZ DENISELLE MC, PASQUINI, DE NICOLA AF, GARAY L

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2018

0953-8194

Changes ofneurosteroids may be involved in the pathophysiology of multiple sclerosis(MS). The present study investigated whether changes of neurosteroidogenesisalso occurred in the grey and white matter regions of the brain in micesubjected to cuprizone-induced demyelination. Accordingly, we compared theexpression of neurosteroidogenic proteins, including steroidogenic acuteregulatory protein (StAR), voltage-dependent anion channel (VDAC) and 18 kDatranslocator protein (TSPO), as well as neurosteroidogenic enzymes, includingthe side chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase/isomerase and 5α-reductase (5α-R), during the demyelination andremyelination periods. Using immunohistochemistry and a quantitative polymerasechain reaction, we demonstrated a decreased expression of StAR, P450scc and 5α-R with respect to an increaseastrocytic and microglial reaction and elevated levels of tumor necrosis factor(TNF)α during thecuprizone demyelination period in the hippocampus, cortex and corpus callosum.These parameters, as well as the glial reaction, were normalised after 2 weeksof spontaneous remyelination in regions containing grey matter. Conversely,persistent elevated levels of TNFα and low levels of StAR and P450scc were observed during remyelinationin corpus callosum white matter. We conclude that neurosteroidogenesis/myelinationstatus and glial reactivity are inversely related in the hippocampus andneocortex. Establishing a cause and effect relationship for the measuredvariables remains a future challenge for understanding the pathophysiology ofMS.