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Melatonin receptor deficiency decreases and temporally shifts ecto-5′-nucleotidase mRNA levels in mouse prosencephalon

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Abstract

Ecto-5′-nucleotidase (eN) is the major extracellular adenosine-producing ecto-enzyme in mouse brain. Via the production of adenosine, eN participates in many physiological and pathological processes, such as wakefulness, inflammation, nociception and neuroprotection. The mechanisms regulating the expression of eN are therefore of considerable neurobiological and clinical interest. Having previously described a modulatory effect of melatonin in the regulation of eN mRNA levels, we decided to analyze the melatonin receptor subtype involved in the regulation of eN mRNA levels by comparing eN mRNA patterns in melatonin-proficient transgenic mice lacking either the melatonin receptor subtype 1 (MT1 KO) or both melatonin receptor subtypes (MT1 and MT2; MT1/2 KO) with the corresponding melatonin-proficient wild-type (WT) controls. By means of radioactive in situ hybridization, eN mRNA levels were found to be diminished in both MT1 and MT1/2 KO mice compared with WT controls suggesting stimulatory impacts of melatonin receptors on eN mRNA levels. Whereas eN mRNA levels increased during the day and peaked at night in WT and MT1 KO mice, eN mRNA levels at night were reduced and the peak was shifted toward day-time in double MT1/2 KO mice. These data suggest that the MT2 receptor subtype may play a role in the temporal regulation of eN mRNA availability. Notably, day-time locomotor activity was significantly higher in MT1/2 KO compared with WT mice. Our results suggest melatoninergic signaling as an interface between the purinergic system and the circadian system.

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Acknowledgments

The authors thank Elke Laedtke and Iris Habazettl for their excellent work and Dr. Hanns Ackermann (Institute for Biostatistics and Mathematic Modelling, Goethe University, Frankfurt am Main, Germany) for his kind help with the statistical analyses.

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Authors and Affiliations

  1. Institute of Anatomy II, Dr. Senckenbergisches Chronomedizinisches Institut (SCI), Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Moran Homola, Martina Pfeffer, Claudia Fischer & Horst-Werner Korf

  2. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, Boston, MA 02215, USA

    Simon C. Robson

  3. Institute of Cell Biology and Neuroscience, Molecular and Cellular Neurobiology, Goethe University, Max-von-Laue-Strasse 13, 60438, Frankfurt am Main, Germany

    Herbert Zimmermann

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  1. Moran Homola
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  2. Martina Pfeffer
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  3. Simon C. Robson
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  4. Claudia Fischer
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  5. Herbert Zimmermann
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  6. Horst-Werner Korf
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Correspondence to Horst-Werner Korf.

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This work was supported by the Dr. Senckenbergische Stiftung, Frankfurt am Main.

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Homola, M., Pfeffer, M., Robson, S.C. et al. Melatonin receptor deficiency decreases and temporally shifts ecto-5′-nucleotidase mRNA levels in mouse prosencephalon. Cell Tissue Res 365, 147–156 (2016). https://doi.org/10.1007/s00441-016-2378-x

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  • DOI: https://doi.org/10.1007/s00441-016-2378-x

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