Neurosteroidogenesis and progesterone anti ‐inflammatory/neuroprotective effects

Progesterone shows anti‐inflammatory and promyelinating effects in mice with experimental autoimmune encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Because neurosteroids have been implicated as protective factors for MS and EAE, we analysed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice, which were then killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage‐dependent anion channel (VDAC), cholesterol side‐chain cleavage (P450scc), 5α‐reductase, 3α‐hydroxysteroid dehydrogenase (3α‐HSOR) and aromatase, whereas changes of 3β‐hydroxysteroid dehydrogenase (3β‐HSD) were not significant. mRNA translocator protein (18 kDa) (TSPO) was elevated, concomitantly with a reactive microgliosis. EAE mice also showed abnormal mitochondrial ultrastructure in axons and neuronal bodies, as well as reduced expression of fission and fusion protein mRNAs. Progesterone pretreatment before EAE induction increased Star, VDAC, P450scc, 5α‐reductase type I, 3α‐HSOR and aromatase mRNAs and did not modify 3β‐HSD. TSPO mRNA was decreased, possibly as a result of reversal of microgliosis. Progesterone pretreatment also improved mitochondrial ultrastructure and increased fission/fusion protein mRNAs. These mitochon...
Source: Journal of Neuroendocrinology - Category: Endocrinology Authors: Tags: REVIEW ARTICLE Source Type: research