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Viral-mediated overexpression of the Myelin Transcription Factor 1 (MyT1) in the dentate gyrus attenuates anxiety- and ethanol-related behaviors in rats

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Abstract

Rationale

Myelin Transcription Factor 1 (MyT1), a member of the Zinc Finger gene family, plays a fundamental role in the nervous system. Recent research has suggested that this transcription factor is associated with the pathophysiology of psychiatric disorders including addiction, schizophrenia, and depression. However, the role of MyT1 in anxiety- and ethanol-related behaviors is still unknown.

Objectives

We evaluated the effects of lentiviral-mediated overexpression of MyT1 in the dentate gyrus (DG) on anxiety- and ethanol-related behaviors in rats.

Methods

We used the elevated plus maze (EPM) and the open field (OF) tests to assess anxiety-like behavior and a two-bottle choice procedure to measure the effects of MyT1 on ethanol intake and preference.

Results

MyT1 overexpression produced anxiolytic-like effects in the EPM test and decreased the number of fecal boli in the OF test, without affecting locomotor activity in both behavioral tests. Next, we demonstrated that ethanol intake and preference were decreased in the MyT1-overexpressing rats with no effect on saccharin and quinine, used to assess taste discrimination, and no effect on ethanol clearance suggesting specific alterations in the rewarding effects of ethanol. Most importantly, ectopic MyT1 overexpression increased both MyT1 and BDNF mRNA levels in the DG. Using Pearson’s correlation, results showed a strong negative relationship between MyT1 mRNA and anxiety parameters and ethanol consumption and a positive correlation between MyT1 and BDNF mRNAs.

Conclusion

Taken together, MyT1 along with being a key component in anxiety may be a suitable candidate in the search of the molecular underpinnings of alcoholism.

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Abbreviations

BDNF:

Brain-derived neutrophic factor

BEC:

Blood ethanol concentration

DG:

Dentate gyrus

EPM:

Elevated plus maze

LV:

Lentiviral vectors

MyT1:

Myelin Transcription Factor 1

NZF-2b:

Neural Zinc Finger 2b

OF:

Open field

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Acknowledgements

The authors would like to acknowledge Mrs. Christine Deforel-Poncet and Dr. Vijay Chandrasekar for their technical assistance with the lentiviral vector preparation. The authors are also grateful to Mr. Mohamed Shafiullah and Dr. Mahmoud Hag Ali from the Central Animal Facility for their advice on animal care and welfare.

Role of the funding source

AB was supported by grants from the United Arab Emirates University (No. NP/13/05) and the National Research foundation (No. 31M082). JLD received grants from the Swiss National Science Foundation 3100-059350 and 3100AO-100686 (JLD). The funders had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Anatomy, Tawam Medical Campus, United Arab Emirates University, Al Ain, UAE

    Amine Bahi

  2. Division of Biochemistry, Department of Medicine, University of Fribourg, 1700, Fribourg, Switzerland

    Jean-Luc Dreyer

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  1. Amine Bahi
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Correspondence to Amine Bahi.

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The authors have no financial interests that might be perceived to influence the results or the discussion reported in this article.

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Bahi, A., Dreyer, JL. Viral-mediated overexpression of the Myelin Transcription Factor 1 (MyT1) in the dentate gyrus attenuates anxiety- and ethanol-related behaviors in rats. Psychopharmacology 234, 1829–1840 (2017). https://doi.org/10.1007/s00213-017-4588-7

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