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

LEICAJ, MARÍA L.; PASQUINI, LAURA A.; LIMA, ANALIA; GONZALEZ DENISELLE, MARIA C.; PASQUINI, JUANA M.; DE NICOLA, ALEJANDRO F.; GARAY, LAURA I.

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2018 vol. 30 p. 1 - 15

0953-8194

Changes of neurosteroids may be involved in the pathophysiology of multiple sclerosis(MS). The present study investigated whether changes of neurosteroidogenesis also oc‐curred in the grey and white matter regions of the brain in mice subjected to cuprizone‐induced demyelination. Accordingly, we compared the expression of neurosteroidogenicproteins, including steroidogenic acute regulatory protein (StAR), voltage‐dependentanion channel (VDAC) and 18 kDa translocator protein (TSPO), as well as neurosteroido‐genic enzymes, including the side chain cleavage enzyme (P450scc), 3β‐hydroxysteroiddehydrogenase/isomerase and 5α‐reductase (5α‐R), during the demyelination and remy‐elination periods. Using immunohistochemistry and a quantitative polymerase chain re‐action, we demonstrated a decreased expression of StAR, P450scc and 5α‐R with respectto an increase astrocytic and microglial reaction and elevated levels of tumor necrosisfactor (TNF)α during the cuprizone demyelination period in the hippocampus, cortex andcorpus callosum. These parameters, as well as the glial reaction, were normalised after2 weeks of spontaneous remyelination in regions containing grey matter. Conversely,persistent elevated levels of TNFα and low levels of StAR and P450scc were observedduring remyelination in corpus callosum white matter. We conclude that neurosteroido‐genesis/myelination status and glial reactivity are inversely related in the hippocampusand neocortex. Establishing a cause and effect relationship for the measured variablesremains a future challenge for understanding the pathophysiology of MS.