کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4338172 | 1614850 | 2012 | 11 صفحه PDF | دانلود رایگان |
In mice with experimental autoimmune encephalomyelitis (EAE) pretreatment with progesterone improves clinical signs and decreases the loss of myelin basic protein (MBP) and proteolipid protein (PLP) measured by immunohistochemistry and in situ hybridization. Presently, we analyzed if progesterone effects in the spinal cord of EAE mice involved the decreased transcription of local inflammatory mediators and the increased transcription of myelin proteins and myelin transcription factors. C57Bl/6 female mice were divided into controls, EAE and EAE receiving progesterone (100 mg implant) 7 days before EAE induction. Tissues were collected on day 17 post-immunization. Real time PCR technology demonstrated that progesterone blocked the EAE-induced increase of the proinflammatory mediators tumor necrosis factor alpha (TNFα) and its receptor TNFR1, the microglial marker CD11b and toll-like receptor 4 (TLR4) mRNAs, and increased mRNA expression of PLP and MBP, the myelin transcription factors NKx2.2 and Olig1 and enhanced CC1 + oligodendrocyte density respect of untreated EAE mice. Immunocytochemistry demonstrated decreased Iba1 + microglial cells. Confocal microscopy demonstrated that TNFα colocalized with glial-fibrillary acidic protein + astrocytes and OX-42 + microglial cells. Therefore, progesterone treatment improved the clinical signs of EAE, decreased inflammatory glial reactivity and increased myelination. Data suggest that progesterone neuroprotection involves the modulation of transcriptional events in the spinal cord of EAE mice.
► Progesterone attenuates signs of experimental autoimmune encephalomyelitis (EAE).
► Progesterone decreases proinflammatory mediators in the spinal cord of EAE mice.
► Progesterone increases transcription of myelin proteins in EAE mice.
► Progesterone increases myelin transcription factors in EAE mice.
► Progesterone exerts direct effects on the spinal cord of EAE mice.
Journal: Neuroscience - Volume 226, 13 December 2012, Pages 40–50