ABSTRACT
The brain 3ß-hydroxysteroid dehydrogenase (3ß-HSD), is the enzyme that catalyzes the biosynthesis of a neuroprotective factor, progesterone. The regulation of 3ß-HSD in response to stress exposure in the cuprizone-induced model of Multiple Sclerosis was investigated and the reaction related to the demyelination extremity. 32 female Wistar rats divided into four groups (i.e., control group (Cont), non-stress cuprizone treated (N-CPZ), physical stress- cuprizone treated (P-CPZ) and emotional stress- cuprizone treated (E-CPZ). A witness foot-shock model used to induce background stress for 5 days. An elevated-plus maze applied to validate the stress induction. Followed by 6 weeks of cuprizone treatment, the Y-maze test performed to confirm brain demyelination. 3ß-HSD gene expression as an indicator of progesterone synthesis examined. At the behavioral level, both stressed groups reflected more impaired spatial memory compared to the N-CPZ group (p < 0.01), with more severe results in the E-CPZ group (p < 0.01). The results of mRNA expression of 3ß-HSD illustrated significant elevation in all cuprizone treated groups (p < 0.001) with a higher up-regulation (p < 0.001) in the E-CPZ group. Background stress -particularly emotional type- exacerbates the demyelination caused by cuprizone treatment. The brain up-regulates the 3ß-HSD gene expression as a protective response relative to the myelin degradation extent.
Subject(s)
3-Hydroxysteroid Dehydrogenases/genetics , Disease Models, Animal , Multiple Sclerosis/enzymology , Psychological Distress , 3-Hydroxysteroid Dehydrogenases/biosynthesis , Animals , Anxiety/pathology , Anxiety/psychology , Cuprizone , Demyelinating Diseases/pathology , Electroshock , Female , Maze Learning , Multiple Sclerosis/genetics , Multiple Sclerosis/pathology , Neuroprotection , Psychomotor Performance/drug effects , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Wistar , Up-RegulationABSTRACT
Multiple sclerosis (MS) is known as the most common demyelinating disease worldwide in which previous studies have shown that stress is a risk factor for the disease's onset and progression. Nevertheless, further studies are needed to investigate the consequences of stress in MS pathology. In this study, after 5 days of exposure to psychological and physical stress as a repetitive distress modality, rats were treated with cuprizone. The demyelination degree was compared in animal groups using Luxol fast blue staining, immunohistochemical staining for myelin basic protein and transmission electron microscopy. Outcomes revealed that animals exposed to stress prior to cuprizone ingestion, elicit more intense demyelination. Continuous psychological distress has more severe effects on myelin sheath destruction in the preclinical stage.
