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The brain 3β-HSD up-regulation in response to deteriorating effects of background emotional stress: an animal model of multiple sclerosis

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Abstract

The brain 3β-hydroxysteroid dehydrogenase (3β-HSD), is the enzyme that catalyzes the biosynthesis of a neuroprotective factor, progesterone. The regulation of 3β-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. 3β-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 3β-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 3β-HSD gene expression as a protective response relative to the myelin degradation extent.

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Data availability statement

Data will be made available on reasonable request.

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Acknowledgments

This research was supported by the Institute of Biochemistry and Biophysics (IBB) at the University of Tehran and did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Laboratory of Neuro-Organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

    Sogol Meknatkhah, Monireh-Sadat Mousavi, Leila Azizzadeh Pormehr & Gholam Hossein Riazi

  2. Department of Chemical Engineering, Faculty of Engineering, University of Tehran, Tehran, Iran

    Pouya Sharif Dashti

Authors
  1. Sogol Meknatkhah
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  2. Monireh-Sadat Mousavi
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  3. Pouya Sharif Dashti
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  4. Leila Azizzadeh Pormehr
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  5. Gholam Hossein Riazi
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sogol Meknatkhah, Monireh-Sadat Mousavi, Pouya Sharif Dashti and Leila Azizzadeh Pormehr. The first draft of the manuscript was written by Sogol Meknatkhah and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gholam Hossein Riazi.

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The authors declare that there are no conflicts of interest.

Ethics approval

The experimental procedures were conducted in accordance with guidelines of the Ethical Committee of the Pasteur Institute of Iran (ECPII) and the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978).

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Meknatkhah, S., Mousavi, MS., Sharif Dashti, P. et al. The brain 3β-HSD up-regulation in response to deteriorating effects of background emotional stress: an animal model of multiple sclerosis. Metab Brain Dis 36, 1253–1258 (2021). https://doi.org/10.1007/s11011-021-00708-5

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