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Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain

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Abstract

NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.

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Acknowledgments

We thank to Katja Lankisch, Natascha Pfeiffer and Christof Dormann for their excellent technical support. This work was supported by a grant from the Olympia-Morata-Programm of the Medical Faculty of the University of Heidelberg to I.I., the Sonderforschungsbereich (SFB) 636/B03 and the German Ministry of Education and Research (BMBF, 01GQ1003B) to P.G.

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Authors and Affiliations

  1. Division of Pediatric Endocrinology, University Children’s Hospital Heidelberg, Heidelberg, Germany

    Ioana Inta & Markus Bettendorf

  2. Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute for Mental Health Mannheim, University of Heidelberg, Heidelberg, Germany

    Miriam A. Vogt, Anne S. Vogel, Peter Gass & Dragos Inta

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  1. Ioana Inta
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  2. Miriam A. Vogt
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  4. Markus Bettendorf
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  6. Dragos Inta
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Correspondence to Dragos Inta.

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Inta, I., Vogt, M.A., Vogel, A.S. et al. Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain. Eur Arch Psychiatry Clin Neurosci 266, 673–677 (2016). https://doi.org/10.1007/s00406-015-0649-2

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  • DOI: https://doi.org/10.1007/s00406-015-0649-2

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