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Title: The Impact of Androstenediol on Remyelination Following Ethidium Bromide-induced Demyelination
Authors: سماح احمد كلخ 
Supervisor: Dr. Abdeslam Mouihate
Keywords: Androstenediol Remyelination Bromide-induced Demyelination
Issue Date: 2014
Publisher:  Kuwait university - college of graduate studies
Abstract: The nervous system is responsible for orchestrating the functions of the different systems of the body. Demyelinating diseases, such as multiple sclerosis, affect the nervous system hindering its normal function. These diseases are characterized by the loss of the myelin sheath around the axons leading to an impaired transmission of electrochemical impulses along the axons. Steroid hormones are potential therapeutic agents for such diseases. In the present study, we investigated the role of the neuroactive steroid androstenediol (ADIOL) on remyelination process. Male Sprague Dawley rats received 2 μl of either sterile saline or the gliotoxin ethidium bromide (EB, 0.04%) into their corpora callosa (CC) using a rat stereotaxic apparatus. These rats received daily subcutaneous injections of either oil or ADIOL (5mg/kg) and their brains were collected at 2 (acute effect), 7 (peak of de-myelination), 14 (start of re-myelination), and 28 (remyelination) days post-EB injection. EB demyelination lesion was assessed using luxol fast blue staining. Immunofluorescent staining was used to explore the impact of ADIOL on the recruitment of oligodendrocyte precursor cells (NG2), maturation of oligodendrocytes (CC-1), the recovery of axons (NF-M), and the recovery of myelin sheath (MBP). Expression levels of total and phosphorylated MBP was also explored using western blot. ADIOL decreased the size of demyelination lesion in the CC at the peak of demyelination 7 days post-EB lesion, and at the start of remyelination 14 days post-EB. ADIOL also enhanced the number of oligodendrocyte precursor cells and promoted an increase in the number of mature oligodendrocytes at the site of the lesion. Administration of ADIOL enhanced the density of myelin fibers (MBP containing fibers) and axons (NF containing fibers) while enhancing the structural organization of myelinated axons in the EB-induced lesion in the CC 14 days post-EB v lesion. ADIOL reduced axonal damage induced by demyelinating effect of EB. ADIOL also promoted phosphorylation of a key MBP protein (18.5kD) 7 days post-EB-induced demyelination. Taken together, these data strongly suggest that ADIOL is endowed with re-myelinating properties in a model of focal gliotoxin-induced demyelination. It induces its beneficial re-myelinating effects through recruitment of oligodendrocytes precursor cells and promotion of their maturation. By inhibiting de-myelination, ADIOL also alleviates the consequent axonal damage.
Appears in Programs:0530 Physiology (M.Sc.)

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